Indirect Inotropic Effect Research Articles

Laterality in direct and indirect inotropic effects of sympathetic stimulation in isolated canine heart.

Although sympathetic nerve stimulation is known to increase ventricular contractility, concomitant increases in heart rate (HR) make it difficult to separate its direct inotropic effect from indirect inotropic effect through a force-frequency mechanism. We stimulated the stellate ganglia in 8 isolated canine hearts with functional sympathetic nerves. Right sympathetic stimulation at 10 Hz increased ventricular end-systolic elastance (E(es)) by 95.7 +/- 7.5% (p < 0.001) and HR by 32.5 +/- 4.2% (p < 0.05). In contrast, left sympathetic stimulation at 10 Hz increased E(es) by 70.7 +/- 6.5% (p < 0.001) without significant changes in HR. Preventing the chronotropic response by fixed-rate pacing attenuated the E(es) response to right sympathetic stimulation at 5 Hz (52.0 +/- 5.1 vs. 22.8 +/- 2.8%, p < 0.001), but not to left sympathetic stimulation at 5 Hz (54.5 +/- 3.4 vs. 53.3 +/- 2.2%, NS). In the isolated canine heart, the right sympathetic nerve affected E(es) by both the direct inotropic effect and the indirect HR-dependent inotropic effect. In contrast, the left sympathetic nerve regulated E(es) primarily by its direct inotropic effect.

The hemodynamic basis for the cardiac effects of parathyroid hormone (PTH) and PTH-related protein.

PTH and PTH-related protein (PTHrP) have been regarded to have positive inotropic effects on the heart as well as positive chronotropic and vasodilator effects. However, inotropy due to a direct effect of these peptides has not heretofore been distinguished from an indirect inotropic effect as a result of altered heart rate or coronary flow. The aim of this study was to determine whether PTH and PTHrP have direct inotropic effects in isolated perfused rat hearts. Three groups of hearts were studied; in all groups, hearts contracted isovolumically and were perfused with a constant coronary pressure. In the control group, heart rate, coronary flow, peak pressure (LVPmax), peak rate of rise of LV pressure (dP/dtmax), and peak intracellular calcium (measured by aequorin) all increased with PTH and PTHrP in a dose-dependent manner. When heart rate was fixed by pacing in a second group of rats, PTH and PTHrP increased coronary flow, LVPmax, and dP/dtmax significantly, indicating that inotropic actions were not mediated solely by chronotropic effects. However, when heart rate was fixed by pacing and, additionally, coronary flow was held constant (by maximal prevasodilation with nitroprusside) in a third group of rats, there was no significant effect of either PTH or PTHrP on LVPmax, dP/dtmax, or peak intracellular calcium. To demonstrate the responsiveness of this latter preparation to inotropic stimulation, the beta-adrenergic agonist, isoproterenol, increased LVPmax, dP/dtmax, and peak calcium even when heart rate was fixed and vasodilation was maximal. Thus, PTH and PTHrP are inotropic agents by virtue of their influence on coronary flow and heart rate, but not by any direct effect on contractile elements in the heart.

Diuretic therapy and exercise performance.

Drugs that induce an increased urine flow are used both legitimately (treatment of hypertension and oedema) and otherwise (rapid weight loss) in sports and exercise. There are 5 major categories of diuretic drugs based on their mechanisms and loci of action. Common to all classes is hypohydration, which has been shown to have an array of adverse effects on performance, including impaired strength, power and endurance. Postural hypotension can be particularly troublesome in the elderly. Also common to all diuretics, except those interfering with the aldosterone mechanism in the distal nephron, is hypokalaemia. Severe symptomatic hypokalaemia (serum K+ concentration less than 3.0 mmol/L) is rare except in clinical situations in which additional hypokalaemic factors are present. Moderate levels of hypokalaemia (serum K+ concentration 3.0 to 3.5 mmol/L) can increase the risk of adverse reactions as has been shown in a variety of prospective clinical studies. Hypokalaemia has effects on cardiac rhythm, muscle function and integrity, local blood flow, carbohydrate metabolism, and the blood lipid profile. Performance studies generally show diminished exercise tolerance in direct proportion to the degree of hypohydration induced. This is not the case, however, in a clinical setting of compromised cardiopulmonary function, in which diuresis has direct and indirect inotropic effects which augment exercise tolerance and decrease symptoms. The ability of the carbonic anhydrase inhibitor, acetazolamide, to induce a hyperventilatory response to the obligatory metabolic acidosis is taken advantage of in mountaineering to prevent or ameliorate the symptoms of acute mountain sickness, thereby improving exercise performance at high altitude. It is suggested that in clinical situations in which the use of a diuretic is considered appropriate, every effort be made to maintain or restore the serum concentration and the total body store of potassium to normal. To some degree this can be accomplished through diet, although potassium chloride supplements or potassium-sparing diuretics or diuretic combinations may be necessary.

The intrinsic innervation of the canine heart: a functional study.

The intrinsic innervation of the heart has been described anatomically but seldom, functionally. These experiments were designed to verify and to evaluate the influence of intrinsic neural activation on the contractility of the atria and ventricles. Nine mongrel dogs underwent total cardiac denervation using the Geis two-stage technique. Following recovery, they were placed on total cardiopulmonary bypass. Balloons were inserted into each cardiac chamber, filled with saline, and used to record atrial and ventricular isovolumic pressures in response to intracoronary drug injections. The hearts were paced to avoid rate changes. Acetylcholine (ACh) (0.05-1.0 mug) was given to assess direct effects on the myocardium; nicotine (NIC) (25-200 mug) was used to produce indirect inotropic effects. d-Tubocurare (dTC) (1.0-2.5 mg) and tetrodotoxin (TTX) (10-30 mug) were used to differentiate the direct and the indirect effects. Both ACh and NIC produced qualitatively similar negative inotropic responses in both atria and ventricles. dTC usually produced a significantly greater blockade of responses to NIC than toACh. TTX administered to 12 other denervated dogs to differentiate direct and neurally mediated responses, completely blocked NIC-induced negative inotropy but did not change responses to ACh. The data show that (1) the intrinsic cardiac innervation can exert significant negative inotropic effects on atria and ventricles (10 to greater than 30%); (2) there is no functional evidence of participation by chromaffin cells in the inotropic responses to intrinsic nerve activation; (3) the negative inotropy produced by NIC is sensitive to dTC and, especially, TTX blockade. This is consistent with the mechanism of action being intrinsic neural stimulation.