Effects of quinidine on vascular resistance and sympathetic nerve activity in humans.

OBJECTIVES: The purpose of the present study was to test the hypothesis that intravenous quinidine, unlike procainamide, causes direct vasodilation and reflexly mediated increases in sympathetic nerve activity. BACKGROUND: Intravenous quinidine can cause significant hypotension. Animal experiments have suggested that quinidine blocks alpha-receptors and also relaxes vascular smooth muscle by a nonadrenergic mechanism. In a recent study we showed that intravenous procainamide causes peripheral vasodilation, hypotension and inhibition of sympathetic nerve activity in humans. Intraarterial procainamide, however, did not cause vasodilation. METHODS: Postganglionic muscle sympathetic nerve traffic was recorded from the peroneal nerve at the fibular head with tungsten microelectrodes, and forearm blood flow was measured with venous occlusion plethysmography. Central venous pressure was measured directly. The direct effects of quinidine on vascular resistance were determined with brachial artery quinidine infusions and measurement of ipsilateral forearm blood flow. RESULTS: In eight normal subjects intravenous quinidine (8 mg/kg body weight infused for 27 min) decreased mean arterial pressure from 87 +/- 3 (mean +/- SE) to 83 +/- 3 mm Hg, central venous pressure from 6.3 +/- 0.6 to 5.0 +/- 0.7 mm Hg and forearm vascular resistance from 32.2 +/- 5.5 to 25.3 +/- 4.7 U (all p < 0.05). Heart rate increased from 67 +/- 4 to 77 +/- 5 beats/min and muscle sympathetic nerve activity from 288 +/- 70 to 660 +/- 151 U/min (both p < 0.05). In five subjects intravenous nitroprusside that caused similar hemodynamic effects produced similar increases in sympathetic nerve activity. In eight subjects graded infusions of quinidine into the brachial artery (0.37, 0.74 and 1.48 mg/min) produced dose-dependent decreases in ipsilateral forearm vascular resistance and marked attenuation of forearm vasoconstriction caused by the cold pressor test. CONCLUSIONS: These data show that quinidine, unlike procainamide, causes vasodilation directly and, when given intravenously, is associated with baroreflex-mediated increases in sympathetic nerve activity.

Transthoracic defibrillation: effect of sternotomy on chest impedance.

The purpose of this study was to determine the effect of sternotomy on transthoracic impedance, a major determinant of current flow and defibrillation success. Transthoracic impedance was determined by using a validated test-pulse technique that does not require actual shocks. Seventeen patients undergoing median sternotomy were studied prospectively. Transthoracic impedance was determined before operation, 3 to 5 days after operation and (in eight patients) greater than or equal to 1 month after operation. When measured using paddle electrodes placed in the standard apex-right parasternal defibrillating position, transthoracic impedance declined after sternotomy in all patients, from 77 +/- 18 to 59 +/- 17 omega (p less than 0.01); smaller declines were demonstrated by using other electrode positions. Transthoracic impedance remained below the preoperative level in the eight patients who underwent a second set of measurements at least 1 month after operation. Six normal subjects not undergoing sternotomy underwent serial transthoracic impedance measurements at least 5 days apart; mean transthoracic impedance did not change. It is concluded that transthoracic impedance declines after sternotomy. At any operator-selected energy level a higher current flow will result after sternotomy; this may facilitate postoperative defibrillation.

Inhibitory effects of procainamide on sympathetic nerve activity in humans.

In experimental animals, procainamide causes hypotension and reductions in efferent vasoconstrictor sympathetic outflow that may result from ganglionic blockade or central nervous system sympathetic inhibition. To test the hypothesis that procainamide decreases sympathetic nerve activity (SNA) in humans, we recorded postganglionic SNA in seven normal subjects in the baseline state and during infusions of procainamide HCl at 50 mg/min (loading) and 8 mg/min (maintenance). At the end of the loading infusion, mean arterial pressure (MAP) had decreased from 88.5 +/- 2.4 (mean +/- SEM) to 81.5 +/- 3.2 mm Hg (p less than 0.05), central venous pressure from 6.7 +/- 0.7 to 5.4 +/- 0.9 mm Hg (p less than 0.05), forearm vascular resistance (FVR) from 28 +/- 4.8 to 22.3 +/- 5.1 resistance units (p less than 0.05), and SNA from 259 +/- 47 to 94 +/- 26 units/min (p less than 0.05). These changes persisted during the maintenance infusion. Increased levels of SNA, FVR, and MAP provoked by the cold pressor test were reduced significantly by intravenous procainamide. In eight other subjects, intravenous procainamide HCl (15 mg/kg at 50 mg/min) caused dose-dependent inhibition of SNA that reversed as blood concentrations fell during drug washout. To determine if procainamide causes direct vasodilation, in nine subjects, graded infusions were delivered into the brachial artery at doses that produced no systemic effect. Ipsilateral FVR tended to increase during local intra-arterial infusion of procainamide. These data show that intravenous procainamide causes hypotension, vasodilation, and sympathetic withdrawal. Vasodilation does not result from a direct vasorelaxant effect of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)