Postextrasystolic potentiation in patients with ischaemic heart disease: influence of inotropic agents.

Abstract

1. The extent of postextrasystolic potentiation (PESP) has been considered a useful parameter for evaluating myocardial contractile reserve in the presence of myocardial stunning or hibernation. Extent of PESP appears to reflect an interaction between myofibrillar calcium concentration and function of the contractile apparatus. However, potential for cardiovascular drugs including agents modifying adenosine 3' 5'‐cyclic monophosphate concentration to influence the extent of PESP in man has not been extensively studied. 2. In 35 patients undergoing diagnostic coronary angiography, we investigated the relationship between the extrasystolic test pulse interval (ETPI) and left ventricular (LV) +dP/dtmax of a postextrasystolic contraction. The influence of three inotropically active agents on this relationship was examined following intravenous bolus injection (metoprolol, 4 mg; sotalol, 20 mg; and milrinone, 1 mg). 3. The patient group examined had predominantly preserved LV function (LVEF 67% with 95% confidence intervals 63%, 71%). In the doses utilized, all agents exerted significant effects on LV+dP/dtmax during atrial pacing: reduction of 12.3% (6.4, 18.2) for metoprolol (P < 0.0005), and 10.9% (4.2, 17.6) for sotalol (P < 0.005); and increase of 11.8% (1.3, 22.3) for milrinone (P < 0.05). 4. With the postextrasystolic interval identical to baseline pacing cycle length, postextrasystolic potentiation of LV+dP/dtmax varied inversely with ETPI. None of the three agents investigated significantly affected this relationship. 5. These results demonstrate that the extent of PESP is unaffected by 'pure' beta‐ adrenoceptor antagonism, (+/‐)‐sotalol or phosphodiesterase inhibition in man. Hence pharmacotherapy with these agents is unlikely to affect assessment of extent of PESP.

Spontaneous Recovery of Myocardial Asynergic Segments Following Acute Myocardial Infarction. The Role of Post-Extrasystolic Potentiation Echocardiography in the Predischarge Evaluation

“…Taken together, these observations render PESP method particularly useful for studying the threshold of inotropic recovery in conditions of reversible contractile dysfunction. Thus, PESP is a potent contractile stimulus dependent on the sarcoplasmic reticulum function and on the calcium sensitivity of contractile proteins [14] . In the ejecting ventricle, the premature beat is followed by a compensatory pause, LV end-diastolic volume may be augmented, and this increased preload contributes to the enhanced performance.…”

“…It has been hypothesized [21][22][23] that Ca 2+ overload during reperfusion turns on endogenous proteases, which attack the myofilaments and decrease their Ca 2+ -responsiveness. However, in some cases, structural abnormalities constitute the main myocardial defect the thin filament complex is reduced, the remaining myofibris as well as the sarcoplasmic reticulum are disorganized, the extracellular matrix proteins accumulate [13,14,24] . However, in some cases, structural abnormalities constitute the main myocardial defect the thin filament complex is reduced, the remaining myofibris as well as the sarcoplasmic reticulum are disorganized, the extracellular matrix proteins accumulate [13,14,24] .…”

“…The partially degraded contractile proteins would have to be replaced by newly synthesized ones in order to repair the myofilaments [21][22][23] . PESP, as a part of the force-interval relation, increases calcium transient and calcium availability at the level of myofibrils [13,14] . The mechanisms underlying myocardial dysfunction after ischaemia-reperfusion myocardial injury may represent the hypothetical basis to make an attempt to explain the difference in intensity of inotropic stimulus enough to improve contraction pattern.…”