Proof for piroximone's inotropic influence: Can it safely be used in coronary artery disease? analysis of end-systolic pressure-volume relations (conductance technique)

Abstract

Improved contractility after applying piroximone (PIR), the new phosphodiesterase-III inhibitor drug, is difficult to prove clinically. However, augmented contractility could increase the risk of myocardial ischemia when used in coronary artery disease (CAD). The analysis of the end systolic pressure-volume relationship (ESPVR) as a load-independent parameter of the contractile left ventricular (LV) function allows for differentiation of PIR's effects: contractility vs unloading. We, therefore analyzed ESPVR and LV function in 16 CAD patients before and after PIR, 0.75 mg/kg intravenously. E_max increased by 39% (9/16 patients) and loops of the ESPVR (16 patients) moved leftward, indicating improved contractility. The delta % changes PIR vs control (16 patients) demonstrated augmentation of LV function via unloading: LV volumes decreased (ESV by 37%, EDV by 19%), LV filling pressure by 34%, and systemic vascular resistance by 19%; dP/dt_max increased by 28%, LV efficiency by 24%, cardiac index by 21%, and ejection fraction by 13%. Pacing-induced anginal threshold increased by 47% after PIR and ischemic postpacing LV filling pressure and ST segment changes tended to normalize under the drug's influence. Thus, PIR improved LV function by both, unloading and positive inotropy. Lack of PIR-induced angina and an increased anginal threshold indicate that the drug can be used safely in CAD patients as well. The analysis of ESPVR proved to be safe and reliable in identifying contractility during the diagnostic cardiac catheterization routine.

Abbreviations

AMI: Anterial myocardial infarction scar
CI (L/min/m²): cardiac index
CON: control
D: (coronary) diagonal branch
EF(%): ejection fraction
ESV (mL): end-systolic volume
EDV (mL): end-diastolic volume
E_max (mmHg/mL): slope k of the ESPVR
ESPVR: end-systolic pressure-volume relation, f-female
IMI: inferior myocardial infarction scar
k (slope) (mmHg/mL): slope k of the ESPVR
LAD: left anterior descending coronary artery
LCX: left circumflex coronary artery
LV: left ventricular
LVEDP (mmHg): LV end-diastolic pressure
LV eff (%): left ventricular efficiency
LVSP (mmHg): LV-systolic pressure
LVW (kg.m): left ventricular work
M: (coronary) marginal branch
m: male
PAM(mmHg): pulmonary artery pressure mean
PIR: piroximone
RCA: right coronary artery
SVR (dyne.s.cm-5): systemic vascular resistance