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.

Clinical, hemodynamic and sympathetic neural correlates of heart rate variability in congestive heart failure.

Heart rate (HR) variability has long been recognized as a sign of cardiac health. In the presence of heart disease, HR variability decreases, an observation that has been associated with poor prognosis in a number of recent studies. HR variability is particularly altered in congestive heart failure (CHF), a condition associated with a number of typical functional hemodynamic and neurohumoral alterations. The relation of measurements of HR variability to these abnormalities in patients with heart failure has not been carefully examined. Twenty-three patients (19 men, 4 women, mean age 49 years) with New York Heart Association class II to IV CHF were studied prospectively without cardiac medications; radionuclide ventriculography, right-sided heart catheterization, peroneal microneurography, plasma norepinephrine and 24- to 48-hour ambulatory electrocardiography were performed. Average RR interval and its standard deviation, and HR power spectrum (0 to 0.5, 0.05 to 0.15 and 0.2 to 0.5 Hz) were derived from the ambulatory electrocardiographic recordings and compared with left ventricular ejection fraction, thermodilution cardiac output, pulmonary arterial wedge pressure, New York Heart Association class, age, muscle sympathetic nerve activity (peroneal nerve) and norepinephrine level by linear regression. None of the measures of HR variability were significantly related to age, left ventricular ejection fraction, cardiac output or functional classification, whereas the 0.05 to 0.15 and 0.20 to 0.50 Hz components were weakly but significantly related to cardiac output (r = 0.49 and 0.42, p = 0.02 and 0.045, respectively). In contrast, a generally stronger and negative relation was demonstrated between spectral and nonspectral measurements of HR variability, and indicators of sympathoexcitation, muscle sympathetic nerve activity and plasma norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Pericardial influence on internal defibrillation energy requirements.

There is no consensus regarding optimal positioning of patch leads for implantation of automatic implantable cardioverter defibrillators. We compared the energy (in joules) required for 50% and 80% successful termination of ventricular fibrillation with titanium-mesh patch leads outside intact normal pericardium and directly on the epicardium in 13 open-chest dogs. Talc was then instilled into the pericardial space to stimulate adhesion formation and pericardial thickening. After 3 weeks of recovery, thoracotomy and defibrillation testing were repeated in nine dogs with the patch leads outside the thickened, adherent pericardium. There were no significant differences in defibrillation energy requirements between locations (p greater than 0.10). In addition, a comparison of electrical impedance measurements at 10 joules showed no significant differences (p greater than 0.30). In this animal model, defibrillation energy requirements were not altered by positioning the patch leads outside normal intact pericardium rather than placing them directly on the epicardium. Furthermore, thickened, adherent pericardium interposed between the patch leads and the heart does not increase defibrillation energy requirements. These data suggest that placement of automatic implantable cardioverter defibrillator patch leads outside the pericardium in patients (including those with pericardial adhesions from previous cardiac operations) will not adversely affect defibrillation efficacy and thus can simplify the implantation procedure.