Phospholamban deficiency does not compromise exercise capacity

Deficiency of phospholamban (PLB) results in enhancement of basal murine cardiac function and an attenuated response to β-adrenergic stimulation. To determine whether the absence of PLB also reduces the reserve capacity of the murine cardiovascular system to respond to stress, we evaluated the heart rate (HR), blood pressure, and metabolic responses of PLB-deficient (PLB−/−) mice to graded treadmill exercise (GTE). PLB−/− mice were hypertensive at rest (125 ± 19 vs. 109 ± 16 mmHg, P < 0.05) but had normal tachycardic and hypotensive responses to isoproterenol. The HR response to GTE was normal; however, the hypertension in PLB−/− mice normalized at peak exercise. Their exercise capacities, as measured by duration of exercise and peak oxygen consumption (V˙o 2), were normal. The oxygen pulse (V˙o 2/HR) curve was also normal in PLB−/− mice, suggesting an ability to appropriately increase stroke volume and oxygen extraction during GTE, despite an inability to increase β-adrenergically stimulated cardiac contractility. Thus deficiency of PLB, although resulting in diminished β-adrenergic inotropic reserve, does not compromise cardiac performance during exercise.

Effects of enhanced ventricular filling on cardiac pump performance in exercising dogs

The extent to which the normal increase in stroke volume during exercise can be augmented by increasing preload by dextran infusion was studied in seven dogs. Each dog ran 3 min on a level treadmill at mild (3–4 mph), moderate (6–8 mph), and severe (9–13 mph) loads during the control study and immediately after 10% dextran 14 ml/kg iv. During severe exercise dextran-augmented stroke volume (+5.4 ml or 19% vs. exercise without dextran, P less than 0.01) and left ventricular end-diastolic diameter and pressure did not change heart rate, aortic pressure, or maximum derivative of left ventricular pressure but decreased systemic vascular resistance by 16%. Similar increases in stroke volume and preload after dextran occurred during mild and moderate exercise when arterial pressure and heart rate were unchanged or increased and systemic vascular resistance was decreased. Thus altering preload above those levels normally encountered during exercise is a potential mechanism to increase stroke volume and cardiac output.

Extrapericardial and esophageal pressures with positive end-expiratory pressure in dogs

Using flat balloon techniques to minimize distortion and artifacts, we studied the effect of positive end-expiratory pressure (PEEP) on local surface pressures between the lung and pericardium overlying the right (R) and left (L) ventricles of ventilated closed-chest anesthetized dogs in right lateral decubitus position. To test the hypothesis that local extrapericardial [Pep(L) and Pep(R)] and average pleural pressures change equally with PEEP, we also measured esophageal pressure (Pes). When 10-cmH2O PEEP was applied, mean increases in Pes, Pep(L), and Pep(R) were 6.2, 5.6, and 5.3 cmH2O, respectively. When PEEP was raised to 20 cmH2O, further average increases in Pes, Pep(L), and Pep(R) were 5.8, 5.0, and 5.4 cmH2O. At each level of PEEP, volume infusion was used to increase stroke volume. Volume infusion at 20-cmH2O PEEP was associated with small 1.0- and 1.5-cmH2O increases in Pep but no change in Pes. Analysis of confidence limits showed that application of up to 20-cmH2O PEEP, with or without volume infusion to restore stroke volume, is associated with nearly equal changes in esophageal and local extrapericardial pressures.

Constancy of stroke volume in ventricular responses to exertion

Diastolic and systolic dimensions of the left ventricle and the free wall of the right ventricle in intact dogs are affected little by spontaneous exercise. The concept that stroke volume and heart rate in normal man increase by about the same relative amounts was derived from estimations of cardiac output, particularly in athletes, based upon indirect measurements using foreign gases or CO2. Data for man obtained with the modern cardiac catheterization or indicator dilution techniques confirm the impression derived from intact dogs that increased stroke volume is neither an essential nor a characteristic feature of the normal cardiac response to exercise. Stroke volume undoubtedly increases whenever cardiac output is increased with little change in heart rate (e.g. in athletes or in patients with chronic volume loads on the heart). Tachycardia produced experimentally with an artificial pacemaker in a resting dog causes a marked reduction in diastolic and systolic dimensions and in the stroke change of dimensions. The factors generally postulated to increase stroke volume during normal exercise may prevent the reduction in stroke volume accompanying tachycardia.