title: Myocardial lactate release after intracoronary verapamil application in humans: acute effects of intracoronary verapamil on systemic and coronary hemodynamics, myocardial metabolism, and norepinephrine levels.
abstract: Coronary and systemic hemodynamic effects of verapamil have been investigated previously in detail. The acute impact of intracoronary verapamil on coronary hemodynamics has, however, not been correlated to simultaneously changes in myocardial metabolism or norepinephrine levels in humans. After bolus application of 1 mg verapamil into the left coronary artery of 52 patients scheduled for routine coronary angiography, heart rate (HR) remained unchanged, 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), calculated from intracoronary Doppler measurements and quantitative coronary angiography, increased after verapamil administration (28.5 +/- 16.7 ml/min to 66.2 +/- 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 baseline and at maximal flow velocity, showed an increase in norepinephrine concentrations in Ao (209 +/- 151 ng/l to 283 +/- 195 ng/l, p < 0.001) and CS (233 +/- 162 ng/l to 323 +/- 248 ng/l, p = 0.004). Myocardial metabolism of pyruvate and free fatty acids were not affected. Glucose release was augmented and initial lactate consumption changed to a net lactate release into the 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 of these metabolites. There was a weak correlation between the increase in CBF 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 the CS at an unchanged metabolism of free fatty acids and pyruvate. One explanation for this unexplained lactate release during increased coronary blood flow might be a wash out phenomenon of lactate from previous ischemic areas, other explanations might be the induction of paradox myocardial ischemia and/or a steal effect. Further studies are necessary to explain these unexpected 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 hemodynamic parameters into account, should be interpreted with caution.
authors.affiliation: Department of Cardiology, University Hospital, Essen, Germany. OOLDENBURG@usamail.usouthal.edu
authors.forename: O
authors.initials: O
authors.lastname: Oldenburg
authors.forename: H
authors.initials: H
authors.lastname: Eggebrecht
authors.forename: A
authors.initials: A
authors.lastname: Gutersohn
authors.forename: J
authors.initials: J
authors.lastname: Schaar
authors.forename: K
authors.initials: K
authors.lastname: Brauck
authors.forename: M
authors.initials: M
authors.lastname: Haude
authors.forename: R
authors.initials: R
authors.lastname: Erbel
authors.forename: D
authors.initials: D
authors.lastname: Baumgart
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007267:Injections; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D002121:Calcium Channel Blockers; D005230:Fatty Acids, Nonesterified; D019344:Lactic Acid; D014700:Verapamil; D009638:Norepinephrine