Effects of low-flow ischemia on the positive inotropic action of angiotensin II in isolated rabbit and rat hearts.

OBJECTIVE: Angiotensin II (ANG II) has recently been reported to increase inotropy in adult rabbit myocytes by a mechanism of alkalinization and consequent increased myofilament sensitivity to calcium. Accordingly, we tested the hypothesis that ANG II would have a greater inotropic effect during ischemic conditions than it would during normoxia, since ischemia-induced intracellular acidosis contributes to ischemic contractile depression by decreasing myofilament calcium sensitivity. METHODS: We studied the effects of ANG II in isolated, red-blood-cell-perfused, isovolumic rat and rabbit hearts during normoxic perfusion conditions and at graded reductions in coronary perfusion pressure (CPP). At each level of perfusion, ANG II was infused at progressively increasing concentrations ranging from 10(-11) to 10(-5) M. The maximal effective ANG II concentration was 10(-7) M. RESULTS: Our studies show that ANG II caused comparable absolute increases in isovolumic LV developed pressure in normoperfused and hypoperfused rabbit hearts. However, since contractile function was markedly depressed in ischemic hearts prior to ANG II administration, the relative inotropic response to ANG II was significantly greater during ischemia than normoxia. Similarly, ANG II had no positive inotropic effect in the rat during normoxia, but increased contractility during ischemia. To assess specifically the potential of ANG II to reverse the negative inotropy of acidosis, normoxic non-ischemic rat hearts were perfused with a hypercarbic acidotic perfusate (pH = 7.1). During the hypercarbic perfusion when contraction was depressed by acidosis, ANG II [10(-7)]M increased LV developed pressure by 19% and +dP/dt by 27% (P < 0.05), in contrast to its lack of intropic effect at a normal pH. The positive inotropic effect observed in rat hearts with ANG II during ischemia was significantly attenuated (P < 0.001) by concomitant infusion with amiloride, 5-(N-ethyl-N-isopropyl) (EIPA), a Na+/H+ exchange inhibitor. CONCLUSIONS: We conclude that during normoxia, ANG II has a different inotropic potency in rabbits from that in rats. In both species, the relative inotropic responsiveness of ANG II is potentiated during low-flow ischemia. These results are consistent with a relative intracellular alkalinization that occurs secondary to ANG II's action to stimulate Na+/H+ exchange.

Myocardial diastolic function and exercise.

There are several important links between aerobic exercise performance and the diastolic phase of the cardiac cycle. During acute exercise, diastolic function must be augmented in order for left ventricular filling to match increased left ventricular output, i.e., cardiac output. This challenges the myocardium because the shortened duration of diastole during exercise may compromise left ventricular filling, thereby limiting the stroke volume. Additionally, left ventricular filling must be accomplished at relatively low filling pressures, otherwise pulmonary vascular congestion may occur. Left ventricular diastolic function may be impaired in the elderly and/or in individuals with ischemic coronary syndromes. Regular aerobic exercise training appears to enhance left ventricular diastolic function and may benefit patients with clinically relevant "diastolic dysfunction." The purpose of this paper is to discuss the relative importance between diastole and exercise and to review some of the involved putative mechanisms.

Exercise training improves left ventricular isovolumic relaxation.

PURPOSE: Left ventricular (LV) diastolic function is an important determinant of aerobic fitness. The purpose of this paper was to investigate the relationship between aerobic fitness and the rate and extent of isovolumic LV relaxation. METHODS: Two series of experiments were performed utilizing both human and animal models. In the first series of experiments, the relationship between LV diastolic time intervals and exercise capacity was assessed in two groups of collegiate men (N = 18) with variable peak run times (Bruce protocol). In the second series of experiments, the extent of LV relaxation was examined in sedentary and exercise-trained rats (treadmill running), using an isolated, isovolumic heart preparation. Subsequent morphological assessment was also performed in rats. RESULTS: At rest, men with greater peak treadmill time had a shorter resting LV isovolumic relaxation time (R-R interval adjusted 1000 ms) (long duration runners, 84+/-5 ms vs short duration runners, 105+/-7 ms, P < 0.05) despite a similar LV diastolic interval. Peak treadmill time was inversely correlated to LV isovolumic relaxation time (R-R interval adjusted 1000 ms) (r = -0.55; P < 0.02). In animal studies (N = 26), the LV pressure-volume relationship was shifted rightward in exercise-trained rats (P = 0.003). Exercise-trained rats had an increased LV inner diameter (sedentary, 5.1+/-0.35 mm vs exercise-trained, 6.1+/-0.28 mm, P < 0.05) and a thicker interventricular septum (sedentary, 1.52+/-0.06 mm vs exercise-trained, 1.72+/-0.09 mm, P < 0.05). CONCLUSION: This study suggests that both the rate and extent of LV isovolumic relaxation is enhanced with exercise training. Further study is required to understand the interrelationship between exercise and diastolic function.

Systolic and diastolic cardiac function time intervals and exercise capacity in women.

PURPOSE: To determine the relationship between exercise capacity and resting cardiac function time intervals in women. METHODS: The noninvasive method of seismocardiography was used to measure resting cardiac intervals in 12 female subjects. On the basis of maximal treadmill time (Bruce protocol), two groups were studied and categorized as long duration runners (LDR; N = 6) or short duration runners (SDR, N = 6). The following resting atrial and left ventricular (LV) cardiac function time intervals were determined: atrial systole, LV systole, LV diastole, LV isovolumetric contraction, LV isovolumetric relaxation, LV ejection, LV preejection, LV filling, LV rapid filling, and Tei index. RESULTS: Heart rate (HR) (65+/-3 vs 61+/-4 b x min(-1) for LDR and SDR, respectively; P = NS) and atrial systolic time (75+/-6 vs 81+/-5 ms for LDR and SDR, respectively; P = NS) were similar between groups. LV systole (348+/-15 vs 302+/-8 ms for LDR and SDR, respectively; P < 0.05) and LV ejection (297+/-13 vs 247+/-7 ms for LDR and SDR, respectively; P < 0.01) were longer in LDR, despite a similar LV isovolumetric contraction time. There was a general trend for a shortened LV diastole in LDR with a significantly shortened LV isovolumetric time in LDR (80+/-8 vs 107+/-8 ms for LDR and SDR, respectively; P < 0.05). LV preejection was shorter in LDR versus SDR (LDR; 114+/-6 vs SDR; 130+/-3 ms, P < 0.05), and the Tei index was less in LDR versus SDR. CONCLUSIONS: Independent of HR, increased treadmill time in young women is associated with greater resting systolic time intervals and decreased diastolic cardiac function time intervals.

Reduced ischemia and reperfusion injury following exercise training.

We examined the effects of two exercise training modalities, i.e., low-intensity endurance and sprint running, on in vitro, isovolumic myocardial performance following ischemia and reperfusion. Rats ran on a treadmill 5 d.wk-1 for 6 wk at the following levels: endurance; 20 m.min-1, 0% grade, 60 min.d-1 and sprint; five 1-min runs at 75 m.min-1, 15% grade interspersed with 1-min active recovery runs at 20 m.min-1, 15% grade. Both endurance and sprint training significantly improved exercise tolerance relative to control (P < 0.05) on two graded exercise tests. Buffer perfused hearts of control (N = 18), endurance (N = 20), and sprint (N = 13) trained animals underwent no-flow ischemia (20 min) and reperfusion (30 min) in a Langendorff mode. During reperfusion, left ventricular developed pressure and its first derivative were 20% higher in sprint (P < 0.05) than either endurance or control hearts. Left ventricular end-diastolic pressure was lowest in sprint during reperfusion (sprint, 10 +/- 1 mm Hg vs endurance, 14 +/- 2 mm Hg; and control, 14 +/- 2 mm Hg, at 30 min reperfusion). Hearts were then used for biochemical studies or dissociated into single cells for measurement of contraction, cell calcium, and action potential duration. Single cell contractions were greatest in sprint despite similar calcium transients in all groups. Ischemia/reperfusion caused action potential prolongation in control but not trained myocytes. Hearts from sprint had the greatest glyceraldehyde-3-phosphate dehydrogenase activity (P < 0.05) and a tendency towards increased superoxide dismutase activity. These results suggest that sprinting increases myocardial resistance to ischemia/reperfusion. This protection may be secondary to increased myofilament calcium sensitivity and/or myocardial expression of glyceraldehyde-3-phosphate dehydrogenase.

The Tei index and exercise capacity.

BACKGROUND: Cardiac function time intervals are known to change with aerobic fitness. Recently, the Tei index of cardiac function [defined as the sum of the isovolumetric contraction (ICI) and isovolumetric relaxation intervals (IRI) divided by the left ventricular ejection time (LVET)] has been proposed to be a very sensitive determinant of cardiac function in patients with cardiomyopathy, i.e. the index is greater in patients with cardiomyopathy than it is in normal subjects. The purpose of this study was to determine the relationship between the Tei index and aerobic endurance in healthy volunteers. METHODS: The relatively new noninvasive method of seismocardiography was used to measure following resting left ventricular (LV) cardiac function time intervals in 51 subjects (18 males and 33 females); Tei index, R-R interval, LV ICI, LV IRI, LVET, LV systole and LV diastole. Designated on the basis of peak treadmill time (Bruce protocol), the following three groups were assigned: Group 1; treadmill time > or = 900 seconds; Group 2: treadmill time ranging from 721 to 899 seconds; and Group 3; treadmill time < 720 seconds. RESULTS: The Tei index value was lower as exercise capacity increased (p < 0.05) primarily due to a reduction in LV IRI (p < 0.05). LVET tended to be longer with increased treadmill time (p < 0.05) but this effect appeared to be secondary to a greater R-R interval in more fit subjects. When adjusted for the R-R interval, a reduced Tei index and LV IRI were still observed in more fit subjects, despite a similar LVET between groups. CONCLUSIONS: Peak treadmill time is inversely related to the Tei index. A reduction of LV IRI appears to be the primary factor in establishing these differences. These data support the important role of LV diastolic function in aerobic fitness.

Perceptions of the heart-rate guide.

Preliminary assessment was made concerning perceptions of the newly developed heart-rate guide, devised as an educational tool to promote physical activity. Unlike the traditional target heart-rate chart, the heart-rate guide illustrates the value of low to moderate intensity physical activity. Following a brief lecture about the Surgeon General's report on physical activity and health and the usefulness of heart-rate charts and guides, 120 college students (M age 21.5 +/- 2.8 yr.) completed a self-report survey consisting of statements regarding their use of target heart rates during exercise and their perceptions of the new heart-rate guide as compared to the traditional heart-rate chart. 83% of the subjects reported that the new guide better illustrated the findings from the Surgeon General's report, 5% reported no difference between the guide and the chart, and 12% reported that the chart better illustrated the report's findings (p < .01). 48% never measure their heart rates when they exercise, 48% sometimes measure their heart rates and 4% always do so (p < .01). While the new guide should not replace the traditional chart, these results suggest that college students perceive the heart-rate guide as a useful tool despite the fact that only a small percentage of students regularly measure their heart rates when they exercise.

Group exercise reduces depression in obese women without weight loss.

Given participation in a 6-mo. exercise and relaxation training 8 obese women showed significant change in scores on the Beck Depression Inventory over the 6-mo. interval, but not on Body Mass Index or Medical Outcome Study Short-Form-36.

Detection of changes in diastolic function by pulmonary venous flow analysis in women athletes.

BACKGROUND: Left ventricular cavity dimension, wall thickness, relaxation, and filling increase with exercise training and have a role in enhancing physical performance. We probed whether changes in diastole may develop separately from those in cardiac morphometry and still contribute to improve physical performance. Challenging diastole by preload reduction with standing and integrating mitral flow analysis with the pulmonary venous flow analysis were viewed as a means for detecting fine diastolic variations. METHODS: Patterns of mitral, tricuspid, and pulmonary venous flow were evaluated by echo Doppler imaging in the supine and standing positions in 11 long-distance runner women athletes participating in training programs and having no or very mild cardiac morphologic alterations and were compared with those in 11 healthy women active in daily life not participating in training programs. Maximal exercise tolerance was tested in both groups with a treadmill with use of the standard Bruce protocol. RESULTS: Echocardiographic left ventricular mass index and mitral and pulmonary flow patterns in athletes and controls were similar while they were supine. Major (P<.01) percent variations and differences between athletes and controls with standing were smaller decrease in right (-12% +/- 5% vs -29% +/- 5%) and left ventricular (-3% +/- 1% vs -9% +/- 2%) dimensions and stroke volume (-7% +/- 4% vs -23% +/- 4%), smaller lengthening of early mitral deceleration (+7% +/- 4% vs +18% +/- 5%), and isovolumic relaxation (-3% +/- 5% vs +15% +/- 7%) times. Athletes showed greater reduction in pulmonary S wave peak velocity (-25% +/- 10% vs -12.5% +/- 7%) and time velocity integral (Si) (-50% +/- 9% vs -21% +/- 8%), greater increases in pulmonary venous diastolic (D) wave peak velocity(+20% +/- 9% vs +12% +/- 10%, meters per second), and time velocity integral (Di) (+81% +/- 16% vs +27% +/- 14%) and greater decrease of S/D(-30% +/- 6% vs -18% +/- 5%) and Si/Di (-70% +/- 10% vs -33% +/- 5%) ratios. At multivariate analysis standing Si/Di was the strongest independent predictor of better exercise tolerance (peak exercise time 1035 +/- 88 sec in athletes, 751 +/- 20 in controls). CONCLUSIONS: Pulmonary flow analysis in athletes while standing can detect changes in diastolic function that are dissociated from apparent left ventricular morphologic alterations, are undetected in the supine position, and may, in part, determine exercise performance.

Brief periods of occlusion and reperfusion increase skeletal muscle force output in humans.

Prolonged periods of ischemia/reperfusion are known to deleteriously affect skeletal muscle performance. However, in animal models, brief bouts of both skeletal and cardiac muscle ischemia/reperfusion have been shown to decrease skeletal muscle injury and increase skeletal muscle force output, a phenomenon termed "preconditioning". Because there are transient periods of ischemia/reperfusion during isometric and concentric muscle contractions, the purpose of this study was to examine how short duration forearm occlusion/reperfusion prior to exercise, influenced isometric skeletal muscle force output in humans. Eleven subjects (6 men and 5 women, mean age 25 +/- 1 years) participated in this study. Using a Biodex multijoint ergometer, a protocol of isolated, isometric forearm wrist flexions was utilized to measure muscle force output in two separate trials. In the first trial, 15 isometric maximal voluntary contractions (MVCs) of the wrist flexors were performed in 20 intervals interspersed with 10 s of rest. In the second trial, forearm occlusion was induced (2 min at 200 mmHg by blood pressure cuff occlusion, with 10 s of hyperemia) prior to exercise. Following cuff occlusion, an identical exercise protocol was followed, i.e. 15 isometric wrist flexor MVCs performed in 20 intervals interspersed with 10 s of rest. The total force output over 15 MVCs was greater following intermittent cuff occlusion (no occlusion 2619 +/- 320 ft.lbs vs cuff occlusion 2986 +/- 195 ft.lbs; p < 0.05). The mean force output per MVC also increased during exercise following intermittent cuff occlusion (no occlusion 174 +/- 21 ft.lbs vs cuff occlusion 199 +/- 13 ft.lbs; p < 0.05). In a second set of experiments, we found a 3 to 4 fold hyperemic blood flow following cuff occlusion. These data suggest that brief periods of cuff occlusion/reperfusion may increase repetitive MVC force output by skeletal muscle. Although further study is needed to fully understand the effects of occlusion/reperfusion on skeletal muscle force output, we hypothesize that, in part, this putative effects is secondary to the hyperemic blood flow which follows cuff occlusion.

The effect of muscle hypoperfusion-hyperemia on repetitive vertical jump performance.

Alterations in skeletal muscle blood flow can greatly influence exercise performance. Brief periods of arterial hypoperfusion and subsequent hyperemia (hypoperfusion-hyperemia) have been shown to decrease the rate of skeletal muscle fatigue in a model of repeated, isometric wrist flexion exercise. However, the mechanism by which hypoperfusion-hyperemia influences dynamic motor skills remains unknown. The purpose of this study was to determine the effects of brief hypoperfusion-hyperemia (by femoral cuff occlusion) on repetitive vertical jump performance. Recreationally trained men and women (n = 10, mean +/- SD age, 25 +/- 2 years), performed 2 randomly assigned jumping trials, each consisting of 40 maximal effort vertical jumps. Jump height was videotaped on a Sony digital video recorder and analyzed with the Scion Images program. Trial 1 consisted of 40 vertical jumps without femoral artery occlusion. Trial 2 consisted of 40 vertical jumps preceded by femoral artery cuff occlusion for 90 seconds at 200 mm Hg, followed by 10 seconds of hyperemia before jumping. For both trials, the rate of decline in power output in men and women was approximately 20%. Hypoperfusion-hyperemia had no significant effect on vertical jumping power output, perhaps because additional muscle groups used to jump vertically (e.g., gluteals and arms) were not occluded. These results warrant further research on the effect of hypoperfusion-hyperemia on strength and power measures.

Brief muscle hypoperfusion/hyperemia: an ergogenic aid?

The purpose of this study was to investigate how short-duration forearm hypoperfusion/hyperemia affects isometric wrist flexion maximal voluntary contraction (MVC) in humans. Fourteen subjects (7 men and 7 women) performed isometric wrist flexion MVC on a Biodex ergometer under 2 experimental conditions: (a) without preceding forearm blood pressure cuff occlusion (control), or (b) immediately following forearm blood pressure cuff occlusion (2 minutes at 200 mm Hg) with 10 seconds of hyperemia (postocclusion). The mean MVC was greater in the postocclusion trial for both men (men, control = 267 +/- 57 J vs. postocclusion = 303 +/- 48 J; p < 0.05) and women (women, control = 185 +/- 21 J vs. postocclusion = 237 +/- 21 J; p < 0.005). The delta MVC between control and postocclusion trials was similarly increased in men and women (men, 36 +/- 13 J vs. women, 52 +/- 11 J; p = not significant [NS] between genders). When men and women were coupled as a single group, the MVC was approximately 20% greater in the postocclusion trial compared with the control trial (control = 226 +/- 31 J vs. postocclusion = 270 +/- 27 J; p < 0.0005). With Doppler/ultrasound imaging, brachial artery flow following 2 minutes of forearm occlusion was five- to sixfold greater than baseline blood flow (p < 0.0005). Isometric wrist flexion MVC is improved in both men and women following brief duration forearm cuff occlusion. The hyperemia that follows cuff occlusion may provide this putative effect.