HEMODYNAMIC EFFECTS OF COMBINED NIFEDIPINE AND SEVOFLURANE IN DOGS WITH AND WITHOUT BLOCKADE OF THE AUTONOMIC NERVOUS SYSTEM

Abstract

S96 INTRODUCTION: Nifedipine, a dihydropyridine Ca2+ channel antagonist, is a potent vasodilator [1] and is used to treat hypertension, coronary and other vasospasm. It may depress cardiovascular function in particular when combined with inhalation anesthetics. These effects may be masked by improved ventricular filling and increase of sympathetic nervous system tone [2]. Thus, this study investigates the effects of nifedipine on cardiovascular function in sevoflurane anesthetized chronically instrumented dogs with and without blockade of the autonomic nervous system (ANS). METHODS: The protocol was approved by the District Government of Munster. Six dogs were chronically instrumented for measurement of heart rate (HR), left atrial (LAP), aortic (ABP) and left ventricular pressure (LVP), LVdP/dt, blood flow velocity (BFV) in the left anterior descending coronary artery (LAD) and myocardial wall thickening fraction. Two experiments were performed in a cross over fashion on separate days: After baseline-registration (BL), sevoflurane anesthesia was induced by mask (Fi=2.5% sevoflurane). In case of ANS blockade 3 mg/kg atropinemethylnitrate, 2 mg/kg propanolol and 20 mg/kg hexamethonium were adminstered i.v. After steady-state conditions, a continuous infusion of nifedipine at a rate of 1 [micro sign]g/kg/min (dose 1) after a loading dose of 50 [micro sign]g/kg followed by a rate of 2 [micro sign]g/kg/min after a loading dose of 75 [micro sign]g/kg (dose 2) was started. Comparisons were made by ANOVA for repeated measures followed by paired t-test with Bonferroni correction. RESULTS: Induction of sevoflurane-anesthesia led to a decrease of MAP. LVdP/dt and WTF and an increase in HR. Bolus injection of nifedipine resulted in a further reduction of MAP, LVdp/dt and WTF only at dose 2. These changes were not present after 30 minutes of infusion. ANS blockade decreased HR, LVdP/dt and MAP. Infusion of nifedipine with ANS blockade led to a decrease of MAP, LVdP/dt and WTF (Table 1).Table 1DISCUSSION: This study demonstrates that nifedipine increases the negative inotropic effects of sevoflurane during ANS blockade in dogs. Slow Ca2+ channel blockers like nifedipine inhibit flux through voltage-dependent Ca2+-channels and decrease intracellular [Ca2+]. The direct effects of Ca2+ channel blockade are attenuated or even reversed in the presence of an intact ANS. This reversal is also present during sevoflurane anesthesia in chronically instrumented dogs with intact autonomic nervous system.