Myocardial lactate release after intracoronary verapamil application in humans: Acute effects of intracoronary verapamil on systemic and coronary hemodynamics, myocardial metabolism, and norepinephrine levels

Coronary and systemic hemodynamic effects of verapamil have been investigat ed previously in detail. The acute impact of intracoronary verapamil on cor onary hemodynamics has, however, not been correlated to simultaneously chan ges in myocardial metabolism or norepinephrine levels in humans. After bolu s application of 1 mg verapamil into the left coronary artery of 52 patient s scheduled for routine coronary angiography, heart rate (HR) remained unch anged, whereas mean arterial blood pressure (MAP) decreased (93.8 +/- 14.9 mmHg to 85.1 +/- 13.7 mmHg, p = 0.001). Coronary blood flow (CBF), calculat ed from intra-coronary Doppler measurements and quantitative coronary angio graphy, increased after verapamil administration (28.5 +/- 16.7 ml/min to 6 6.2 +/- 41.8 ml/min, p < 0.001), whereas coronary vascular resistance index (CVRI) decreased (1.43 +/- 0.92 to 0.46 +/- 0.23, p <0.001). Blood samples , taken simultaneously from the aorta (Ao) and coronary sinus (CS) at basel ine and at maximal flow velocity, showed an increase in norepinephrine conc entrations in Ao (209 +/- 151 ng/I to 283 +/- 195 ng/l, p <0.001) and CS (2 33 +/- 162 ng/l to 323 +/- 248 ng/l, p = 0.004). Myocardial metabolism of p yruvate and free fatty acids were not affected. Glucose release was augment ed and initial lactate consumption changed to a net lactate release into th e CS (Ao to CS differences: glucose: -1.92 +/- 9.9 mg/dl to -12.8 +/- 22.8 mg/dl, p < 0.001; lactate: 0.07 +/- 0.2 mmol/l to -0.08 +/- 0.3 mmol/l, p = 0.001). Similar results were obtained for the extraction ratios and flux o f these metabolites. There was a weak correlation between the increase in C BF and lactate release into the CS. This is the first report of unexpected myocardial lactate release following intracoronary verapamil administration in humans. This lactate release was paralleled by an increased glucose release into th e CS at an unchanged metabolism of free fatty acids and pyruvate. One expla nation for this unexplained lactate release during increased coronary blood flow might be a wash out phenomenon of lactate from previous ischemic area s, other explanations might be the induction of paradox myocardial ischemia and/or a steal effect. Further studies are necessary to explain these unex pected findings of increased coronary flow and myocardial lactate release. Until reliable explanations are pending, studies using only lactate release as a marker of myocardial ischemia, without taken coronary and systemic he modynamic parameters into account, should be interpreted with caution.