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J Appl Physiol 99: 2121-2127, 2005. First published July 21, 2005; doi:10.1152/japplphysiol.01212.2004
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Sprint training improves postischemic, left ventricular diastolic performance

Joseph R. Libonati,1,2,3 Zebulon V. Kendrick,1 and Steven R. Houser2,3

Departments of 1Kinesiology and 2Physiology and 3Cardiovascular Research Center, Temple University, Philadelphia, Pennsylvania

Submitted 17 November 2004 ; accepted in final form 20 July 2005


   ABSTRACT
TOP
 ABSTRACT
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
We examined the effects of sprint training on left ventricular diastolic stiffness during normoxia and after ischemia-reperfusion (I/R). Thirty-seven, male Sprague-Dawley rats, weighing 150–175 g at the initiation of the experiment, were randomly assigned to a sedentary, control group (n = 20) or to a high-intensity, sprint-trained group (n = 17). Animals were trained 5 days/wk on a motor-driven treadmill for 6 wk. High-intensity sprint training consisted of running five 1-min sprints at 75 m/min, 15% grade, interspersed with 1-min active recovery runs at a speed of 20 m/min, 15% grade. Langendorff-derived isolated heart performance was measured before and after 20 min of no-flow ischemia followed by 30 min of reperfusion. Isolated myocytes were harvested from a subset of postischemic hearts. Sprint training reduced Langendorff-derived LV chamber stiffness (P < 0.05) and induced a rightward shift in the LV pressure-volume relationship during both normoxic perfusion and after I/R. LV developed pressure after I/R was also better preserved in hearts obtained from sprint-trained animals (P < 0.05), a result that is in part related to a lower postischemic LV chamber stiffness in sprint-trained hearts. The putative impact of sprint training on postischemic LV chamber stiffness was masked by glycolytic inhibition with iodoacetate, suggesting that glycolysis was involved in the better postischemic recovery observed in sprint-trained hearts. There was a tendency for enhanced postischemic cardiomyocyte shortening in sprint-trained cardiomyocytes compared with control. The rate of myocyte relaxation, i.e., time for 50% relaxation of the Ca2+ transient amplitude, was similar between groups. These data suggest that additional mechanisms unrelated to Ca2+ were involved in sprint-induced protection from ischemia-reperfusion-induced LV diastolic dysfunction.

diastole; glycolysis; heart; exercise

LEFT VENTRICULAR (LV) diastolic performance and peak oxygen consumption are closely related (26, 36, 40). Traditional endurance exercise training has been shown to reduce LV stiffness (44, 45) and induce a rightward shift in the LV pressure-volume relationship (24, 25). This is a significant issue, because a lower LV stiffness during conditions of normal perfusion may, in turn, protect the myocardium from ischemia-related LV diastolic dysfunction. Clinically, an elevation in LV diastolic stiffness is a hallmark sign of ischemic heart disease (2, 3, 13). In general, chronic aerobic exercise training has been shown to protect the myocardium from ischemia-reperfusion (I/R) injury (38). Several studies have shown that training protects the myocardium from hypoxia, anoxia, and I/R injury (4–8, 18, 19, 21, 27, 29, 32, 35) with higher intensities of exercise shown to confer greater protection (6, 7, 27).

Myocardial glycolytic flux is accelerated with acute bouts of high-intensity exercise and is perhaps likely to induce a more prolific training effect in the glycolytic cascade than are lower intensities of exercise. Upregulation of glycolytic flux has been proposed to explain why higher intensities of exercise training are protective from I/R injury (20, 27). For example, in our laboratory's previous study, GAPDH activity was higher in cardiomyocytes harvested from sprint-trained compared with endurance-trained hearts (27). Although ATP derived from glycolysis elicits only a small proportion of total myocardial ATP generation, its cellular compartmentalization makes it functionally important in protection from I/R injury, in part, by maintaining ionic balance (11, 17). For example, ATP derived from glycolytic metabolism is thought to preferentially fuel Ca2+ uptake by the sarcoplasmic reticulum (33, 46), the Na+-K+ pump (14), and the ATP-sensitive K+ channel (43). With respect to the later, exercise training has specifically been shown to blunt the responsiveness of the sarcolemmal ATP-sensitive K+ channels to anoxia (18) and improve the myocardial sensitivity to glibenclamide, an ATP-sensitive K+ channel inhibitor (19). Exercise training has also been shown to enhance myocardial antioxidant scavenging (27, 34) and increase the expression of 72-kDa heat shock protein (HSP72) (12, 28), which is also capable of regulating ATP-sensitive K+ channel conductance (16). Moreover, ATP derived from glycolysis plays an important role in actin-myosin rigor-bond dissociation (1–3, 41), a factor critical in regulating myocardial diastolic function.

Clearly, there is a complex interplay of mechanisms associated with how exercise training protects the heart from I/R contractile dysfunction (38).

However, only limited data are available with respect to how training specifically impacts LV diastolic function (7, 19, 27). We hypothesized that high-intensity sprint training would protect the heart from ischemia-induced elevations in LV diastolic chamber stiffness by upregulating glycolysis. The purpose of the present study was to investigate the impact of high-intensity sprint running on isolated heart and cardiomyocyte function after no-flow I/R.


   METHODS
TOP
 ABSTRACT
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Exercise Training

Thirty-seven, male Sprague-Dawley rats, weighing 150–175 g at the initiation of the experiment, were randomly assigned to a sedentary, control group (n = 20) or to a high-intensity, sprint-trained group (n = 17). Rats were maintained and treated in accordance with the guidelines from the American Physiological Society. Rats were housed three to four per cage, maintained on a 12:12-h light-dark cycle, and fed ad libitum (Purina Rat Chow, Richmond, IN).

As previously described (27), animals were trained 5 days/wk on a motor driven treadmill for 6 wk (Quinton Instruments, Seattle, WA). High-intensity sprint training consisted of running five 1-min sprints at 75 m/min, 15% grade, interspersed with 1-min active recovery runs at a speed of 20 m/min, 15% grade. Rats in the sprint-trained group were acclimated to the treadmill for 2 wk, in which the speed and grade were gradually increased until the final intensity was reached. Rats were run between 0700 and 1100 daily. To maintain familiarity with the treadmill, the sedentary control group exercised once per week at a speed of 20 m/min, 0% grade, for 5–10 min.

Graded Exercise Tolerance Test

As previously described, the effectiveness of exercise training was determined by treadmill performance on a graded treadmill test (15). Performance on the graded treadmill tolerance test was expressed in kilogram times meters (kg·m) where: kg·m = body wt (kg) x treadmill speed (m/min) x duration of the exercise (min) x percent elevation of the treadmill.

Isolated Heart Experiments

As previously described (27), isolated heart experiments were performed at least 48 h after the exercise tolerance test. Rats were anesthetized with pentobarbital sodium (50 mg/kg of body wt ip) weighed and treated with heparin (1,000 U/kg body wt). A thoracotomy was performed through the midline of the sternum, the aorta was cannulated, and in situ retrograde perfusion of the coronary arteries was started. The heart was removed and trimmed of excess tissue, weighed, and transferred to a Langendorff apparatus where it was perfused in vitro with a modified Krebs-Henseleit solution containing (in mM) 1.25 CaCl2, 130 NaCl, 5.4 KCl, 11 dextrose, 2 pyruvate, 0.5 MgCl2, 0.5 NaH2PO4, and 25 NaHCO3, and aerated with 95% oxygen and 5% carbon dioxide, pH 7.35–7.4. Hearts were perfused at 37°C with constant coronary perfusion pressure (100 cmH2O). An incision was made in the left auricle, and a drainage cannula (PE tubing) was inserted through the mitral valve into the apex of the left ventricle for drainage of thebesian flow. Coronary flow rate was measured by timed collection of the myocardial effluent.

A latex balloon filled with saline was inserted into the LV and was attached to a pressure transducer (Statham 23dB Gould, Oxnard, CA) and a chart recorder (Gould) to measure LV pressure and record its first derivative (rate of pressure development). The heart was electrically paced at 5 Hz via silver electrodes. The balloon volume of all hearts was adjusted to elicit an LV end-diastolic pressure of 10 mmHg during equilibration. Each heart was allowed to equilibrate for at least 20 min, at which point preischemic baseline measurements were recorded.

Incremental LV balloon volume infusions of 10–25 µl were performed during normoxia and after I/R. The LV systolic and LV end-diastolic pressures were measured at each volume increment (13). The measured change in systolic pressure per change in LV volume was determined for each heart up to a plateau in systolic pressure development, and it was expressed as the LV active tension coefficient. Also, for each heart, the measured change in LV end-diastolic pressure per change in LV volume was determined and expressed as the LV chamber stiffness coefficient. The mean LV chamber stiffness coefficients ({Delta}LV pressure/{Delta}LV volume, where {Delta} is change) are shown in Fig. 1. Moreover, to graphically illustrate the combined LV systolic and end-diastolic pressure volume relationships in both groups before and after I/R, the LV systolic pressure-volume relationships were linearly curve fit while the LV end-diastolic pressure-volume relationships were exponentially fit.



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  		Fig. 1. Left ventricular (LV) diastolic chamber stiffness in control and sprint-trained hearts during preischemia (white bars), postischemia (black bars), and postischemia + iodoacetate (gray bars). Values are means ± SE. Sprint-training reduced the pre- and postischemic LV diastolic chamber stiffness. Reperfusion with iodoacetate significantly increased LV chamber stiffness in sprint but not control. NS, not significant.

 
After determination of the baseline LV pressure-volume relationship, the LV balloon volume was then readjusted to elicit an LV end-diastolic pressure of 10 mmHg and held constant throughout the period of I/R. The I/R protocol consisted of 20 min of no-flow ischemia followed by 30 min of constant-pressure reperfusion (100 cmH2O). Reperfusion was performed in the absence or presence of 0.5 mM iodoacetate (IAA). The duration of ischemia was chosen to induce transient elevations in LV end-diastolic pressure without inducing overt systolic dysfunction at 30 min of reperfusion. After 30 min of reperfusion, a postischemic LV pressure-volume relationship was reestablished.

Myocyte Isolation

After the I/R protocol, LV myocytes were isolated from hearts (control, n = 5; sprint trained n = 3), using cell-isolation techniques previously reported in detail (42). Briefly, hearts were perfused with a Ca2+-free Krebs-Henseleit buffer with collagenase (180 U/ml) (KH-C). When the heart softened, the right and left ventricles were dissected, and the left ventricle was minced in the remaining KH-C solution. LV cells were placed in a shaking water bath at 37°C for 5 min and then filtered. The resulting solution was then centrifuged and resuspended in Krebs-Henseleit solution containing bovine serum albumin (1%) and 1 mM Ca2+. The cell suspensions were kept at room temperature and gassed with 95% O2 and 5% CO2 to maintain a pH of 7.4. All experiments were conducted within 6 h of isolation.

Myocyte Contraction Magnitude

Myocytes were superfused with a normal Tyrode solution containing (in mM) in 150 NaCl, 5.4 KCl, 1.2 MgCl, 10 glucose, 2.5 Na+-pyruvate, 5 HEPES, and 1 mM Ca2+, pH 7.4, and incrementally stimulated at 0.5, 1.0, 1.5, and 2.0 Hz at 37°C. Cell length was measured by placing an infrared filter (715 nM; model 3145, Twardy) in the bright-field path. The red image was detected by a low-threshold, infrared sensitive television camera (model 4800, Cohu, San Diego, CA) mounted in an eyepiece port. The cell image was displayed on the television monitor (Panasonic, New York, NY), and myocyte contractions were recorded using a video-based edge detector (Crescent Electronics, Salt Lake City, UT). The cell length at peak shortening during each beat was divided by the diastolic cell length for that beat and expressed as percent resting cell length. All data were recorded continuously on a chart recorder (Gould, Oxnard, CA).

Indo-1 Measurements

Myocytes were loaded with indo-1 by incubation with the acetoxymethyl ester of indo-1 (indo-1 AM). The cell suspension in Krebs-Henseleit buffer (0.5 ml) was mixed with 22 µl of a premixed solution containing 18.75 µl fetal calf serum, 0.625 µl of 25% (wt/wt) Pluronic F127 (in dimethyl sulfoxide), and 2.5 µl of 1 mM indo-1 AM (in dimethyl sulfoxide). The final indo-1 concentration was 4.8 µM. Myocytes were loaded for 2.5 min and then superfused with Tyrode solution (150 NaCl2, 5.4 KCl, 1.2 MgCl2, 10 glucose, 2.5 Na+-pyruvate, and 5 HEPES, pH 7.4) with 1 mM Ca2+ for 10 min. This loading procedure ensured that cytosolic indo-1 AM was almost completely hydrolyzed and minimized the compartmentalization of indo-1.

Flurorescence experiments were performed using a Zeiss inverted microscope equipped for epifluorescence measurements. Excitation was initiated at 350 nm (10-nm bandwidth excitation wavelength with an interference filter; model P10–350-F-G833, Corion). A 460-nm dichoric mirror split the fluorescence emission beam, and the emission at 410 nM (the emission peak of the Ca2+ + bound form of the dye: I 410) and 480 nM (the emission peak of the Ca2+-free form of the dye: I 480) were directed to two photomultiplier tubes (model R-1527, Hamamatsu, Houston, TX) via interference filters (10-nm bandwidth; model 53805 and 53850, respectively, Oriel). Photomultiplier tube outputs were displayed on photometers (2426 systems, Pacific Instruments, Trenton, NJ) in photon counts per second and sent to an analog divider for instantaneous computation of the ratio of fluorescence at two wavelengths (I 410/I 480). System background, including average unloaded cell background, was subtracted on the divider. The uncalibrated cytosolic Ca2+ was represented by I 410/I 480. The magnitude of the Ca2+ transient was calculated as the diastolic indo-1 ratio subtracted from the peak systolic indo-1 ratio. All cardiomyocytes were studied under steady-state sarcoplasmic reticulum Ca2+ loads.

Data Analysis

Data are reported as means ± SE. Physical characteristics, exercise test performance, and baseline isolated heart performance were compared with Student's independent t-tests. LV chamber stiffness during normoxia and I/R was compared with one-way ANOVA and adjusted least significant difference post hoc analysis. Reperfusion performance and isolated cell data were compared with ANOVA with repeated-measures and adjusted least significant difference post hoc analysis. Data analysis was performed with SPSS (SPSS, release 12). Differences among groups were considered significant if P ≤ 0.05.


   RESULTS
TOP
 ABSTRACT
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Animal Characteristics

As illustrated in Table 1, body weight, heart weight, and heart weight-to-body weight ratio were similar between control and sprint-trained animals. Sprint-trained animals showed better exercise performance on the graded exercise tolerance test relative to control animals.


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  		Table 1. Animal characteristics and baseline Langendorff performance

 
Isolated Heart Performance

Preischemia.   At baseline, the Langendorff isolated heart performance was similar between groups at a fixed LV end-diastolic pressure of 10 mmHg (Table 1). However, when preischemic Langendorff performance was assessed over a range of LV filling volumes, LV diastolic chamber stiffness was less in sprint relative to control animals (P < 0.05; Fig. 1). Moreover, the LV end-diastolic pressure-volume relationship was directionally shifted rightward in sprint-trained animals (Fig. 2A). The rightward shift in the LV end-diastolic pressure volume relationship among sprint-trained animals is similar to a previous report showing a rightward shift in the LV end-diastolic pressure-volume relationship with endurance training (25). The LV systolic pressure-volume relationship, i.e., active tension development, was also shifted rightward in sprint vs. control hearts (Fig. 2A), because the active tension coefficient was greater in control vs. sprint-trained hearts (control: 5.06 ± 0.03 mmHg/µl vs. sprint: 4.01 ± 0.03 mmHg/µl; P < 0.05). Despite the rightward displacement of the systolic and diastolic pressure-volume relationships, peak LV developed pressure was similar between groups.



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  		Fig. 2. LV systolic and diastolic pressure-volume relationships preischemia (A) and post-ischemia (B). Sprint training shifted the LV end-diastolic pressure (LVEDP)-volume relationship rightward in both conditions. Dashed lines, control; solid lines, sprint.

 
Postischemia.   Our model of 20 min of no-flow ischemia was chosen to elicit near full systolic functional recovery during reperfusion. Although both groups showed prompt recovery of LV developed pressure after ischemia, hearts from sprint-trained animals showed better functional recovery of LV developed pressure relative to control hearts throughout reperfusion (Fig. 3). LV developed pressure was greater in sprint, in part, because LV end-diastolic pressure (at the fixed, preischemic LV end-diastolic volume used to elicit an LV end-diastolic pressure of 10 mmHg) was lower throughout reperfusion (Fig. 4).



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  		Fig. 3. Time course recovery of LV developed pressure as a percent change from baseline during reperfusion. Values are means ± SE. Sprint-trained hearts showed nearly full recovery by 10 min of reperfusion and exceeded the LV performance of control throughout reperfusion. *P < 0.05.

 


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  		Fig. 4. Time course recovery of LVEDP during reperfusion. Values are means ± SE. LVEDP was lower in sprint-trained hearts relative to control hearts throughout reperfusion. *P < 0.05.

 
Sprint-trained hearts were also able to generate greater LV developed pressures throughout the pressure-volume relationship (Fig. 2B). The postischemic active tension coefficient was blunted to a similar extent in control and sprint-trained hearts relative to preischemic values (Fig. 2B). As depicted in Fig. 1, hearts from sprint-trained animals showed a lower LV diastolic chamber stiffness relative to control hearts. Thus the enhanced postischemic functional recovery in sprint was largely due to a better preservation of LV diastolic function, i.e., a lower LV chamber stiffness, and was moderately correlated with preischemic LV chamber stiffness (r = 0.61, P < 0.05). The preservation of LV chamber stiffness in postischemic sprint-trained hearts was attenuated after reperfusion with IAA (Fig. 1), but IAA infusion did not significantly impact LV chamber stiffness in control hearts. Because IAA is a known inhibitor of the key glycolytic enzyme GAPDH, these data suggest that glycolysis was, in part, involved in the enhanced I/R LV diastolic recovery observed in sprint-trained hearts. One hypothesis is that glycolysis may reduce Ca2+ overload and enhance isolated cardiomyocyte relaxation.

Myocyte contraction, time for 50% relaxation, and Ca2+ transients.   We examined indexes of cardiomyocyte function and the Ca2+ transient in isolated cardiomyocytes at incremental stimulation frequencies. Figure 5A shows that the magnitude of cell shortening tended to be greater in sprint-trained cardiomyocytes relative to control cardiomyocytes over the entire range of stimulation frequencies (group main effect P = 0.07). Interestingly, we did not observe a negative treppe phenomenon sometimes characteristic of rat cardiomyocytes not exposed to I/R at these stimulation frequencies. Figure 5B illustrates that T50 was similar between control and sprint-trained myocytes. Moreover, the Ca2+ amplitude was also similar in control and sprint-trained myocytes over the range of stimulation frequencies (Fig. 5C).



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  		Fig. 5. Isolated myocytes. Isolated myocytes were harvested from postischemic hearts and incrementally paced from 0.5 to 2 Hz. A: magnitude of cell shortening. B: time for 50% relaxation rates (T50). C: calcium transient amplitude. Dashed lines, control; solid lines, sprint. Values are means ± SE. Myocytes from sprint-trained hearts had tendency for a higher (P = 0.07) cell shortening at all stimulation frequencies. T50 relaxation and magnitude of the calcium transient were similar between groups.

 

   DISCUSSION
TOP
 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The major findings of this study are that, similar to endurance training (25), sprint-training reduced Langendorff-derived LV chamber stiffness and induced a rightward shift in the LV pressure-volume relationship during both normoxic perfusion and after no-flow I/R. Interestingly, preischemic LV chamber stiffness was moderately correlated with postischemic LV chamber stiffness. LV developed pressure after I/R was also better preserved in hearts obtained from sprint-trained animals, a result that was in part due to a lower postischemic LV chamber stiffness in sprint, because postischemic systolic function, i.e., the active tension coefficient, was similar between groups. Both the rate and extent of myocyte relaxation are important in establishing the LV diastolic performance (13). Our data in isolated hearts suggest that the extent of relaxation was improved with sprint-training during normoxia and after I/R, an effect independent of extrinsic factors such as neurohormones, heart rate, and pericardial restraint.

The putative impact of sprint training on postischemic LV chamber stiffness was masked by glycolytic inhibition with IAA. Reperfusion with IAA did not alter LV diastolic chamber stiffness in control hearts, suggesting that glycolysis was, in part, involved in the better postischemic recovery observed in hearts from sprint-trained animals. Although several reports have suggested that ATP derived from glycolysis is protective from I/R injury (1–3, 10, 17, 22, 41), it remains unclear from these reports whether glycolysis per se confers postischemic protection directly via ATP hydrolysis (2, 41) or indirectly by maintaining Ca2+ balance and subsequent myofilament Ca2+ sensitivity (3, 11, 23). In this context, our results are not in agreement with working heart data presented by Burelle et al. (9), who showed that moderate-intensity treadmill running reduced the rate of glycolysis before and after ischemia when the perfusate contained 5.5 mM glucose. The differences between the present study and data by Burelle et al. may be due to the differences in factors such as the exercise intensity, isolated heart models, or perfusate glucose concentrations.

The present experiments in isolated cardiomyocytes show that there was a tendency for postischemic cardiomyocytes obtained from sprint-trained hearts to have a greater cell shortening at a given Ca2+ transient relative to control. However, the rate of myocyte relaxation, i.e., T50 at a given Ca2+ transient, was similar between groups, suggesting that mechanisms unrelated to Ca2+ were involved in sprint-induced protection from I/R-induced LV diastolic dysfunction.

One plausible explanation for these findings is that sprint-training increased glycolytic ATP availability for rigor bond dissociation (2, 41). ATP depletion secondary to I/R may cause prolonged actin-myosin interaction during diastole by failing to bind and dissociate actin and myosin during the final stage of the cross-bridge cycle (41). Micromolar disturbances in cytosolic ATP are known to impact actin-myosin dissociation. Moreover, ATP depletion secondary to I/R may also alter intracellular Ca2+ concentration by limiting ATP availability to energy-dependent ion pumps. Corretti et al. (11) set forth the hypothesis that free radical accumulation during I/R inhibits GAPDH, perpetuates intracellular Ca2+ overload, and induces subsequent reductions in myofilament Ca2+ sensitivity. In our laboratory's previous study, we showed that superoxide dismutase and GAPDH were upregulated in myocardium from sprint-trained animals (27). Along these lines, Bowles and Starnes (7) showed that high-intensity treadmill running reduced intracellular Ca2+ overload and improved myofibrillar Ca2+ responsiveness in postischemic hearts. In another study, Bowles et al. (6) also demonstrated that high-intensity treadmill running preserved ATP content in postischemic myocardium and that postischemic ATP content was highly correlated with postischemic systolic functional recovery. With respect to LV diastolic function, studies by Bowles and Starnes (7) and Jew and Moore (19) have shown that post-ischemic LV diastolic stiffness was reduced with training. The mechanisms behind these results are difficult to interpret however. In the study by Bowles and Starnes (7), postischemic 45Ca2+ uptake was less in trained vs. sedentary hearts, whereas Jew and Moore (19) observed a higher postischemic myocardial Ca2+ content in trained hearts (7, 19).

Although not measured in the present study, another speculative possibility by which sprint training conferred protection from I/R dysfunction is through its impact on heat shock proteins. Recent data have shown that HSP72 is upregulated with exercise training, an effect that can occur within a few days of training (12, 28, 31). HSP72 is associated with a host of protective mechanisms, including stabilizing and refolding damaged proteins during stressful conditions like ischemia. Interestingly, it has been suggested that HSP72 protection from I/R injury is, in part, mediated via its effects on ATP-sensitive K+ channels (16).

Jew and Moore (19) have recently shown that exercise training improves the myocardial sensitivity to glibenclamide, an ATP-sensitive K+ channel inhibitor. In their study, 20 wk of endurance training reduced LV chamber stiffness after I/R (19). Reperfusion with glibenclamide, however, only attenuated ischemia-induced elevations in LV diastolic stiffness in sedentary hearts, suggesting an important role for the ATP-dependent K+ channel in training-induced protection against I/R LV diastolic dysfunction. Jew and Moore (18) have also shown that exercise training delays the expression of ATP-sensitive K+ current during anoxia. Given the functional connection between glycolysis and the ATP-sensitive K+ channel (43), perhaps training improves postischemic LV diastolic function via ATP-dependent substrate interaction with the ATP-sensitive K+ channel (30).

The present data show that postischemic systolic contractile function remained somewhat stable, whereas diastolic stiffness increased in control hearts. This may have occurred secondary to the heterogeneous responsiveness of LV cardiomyocytes to I/R (39). Some postischemic myocytes may be in rigor, whereas others are not. Thus postischemic cells in rigor may induce a stretch on adjacent myocytes causing increased compensatory contraction of these myocytes via the Frank-Starling mechanism thereby maintaining systolic pressure generation (41).

Potential Limitations

Neither high-energy phosphate content nor metabolic flux was directly measured in this study, making it difficult to generate any categorical conclusions with respect to the contribution glycolysis plays in training-induced cardioprotection from I/R injury. Attempting to pair data from Langendorff isolated hearts with isolated cardiomyocytes is also of issue, because the isolated cardiomyocyte model selectively examines only healthy, surviving myocytes within the sample. Thus injured cells that contributed to Langendorff-derived performance are not well represented in the isolated cardiomyocyte data. Along these lines, it is also important to note that the metabolic status of isolated cardiomyocytes may have changed during the interval from isolation to analysis, and the Ca2+ indicator indo-1 may not specifically reflect troponin C-bound calcium. Also, important calcium regulatory proteins such as the Na+/Ca2+ exchanger were not measured in the present study. Song et al. (37) showed that sprint training reduced Na+/Ca2+exchange activity in postinfarction myocytes, which may alter Ca2+ regulation during ischemia and reperfusion (37).

In summary, we conclude that sprint-training protects the myocardium from I/R dysfunction, in part, by preserving LV diastolic function. More work is necessary to elucidate the cellular mechanisms associated with exercise training and I/R.


   FOOTNOTES
 

Address for reprint requests and other correspondence: J. R. Libonati, Temple Univ., 122 Pearson Hall, 1800 North Broad St., Philadelphia, PA 19122 (e-mail: jlibonat{at}temple.edu)

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


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 ABSTRACT
 METHODS
 RESULTS
 DISCUSSION
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