Effects of alpha adrenergic blockade upon coronary hemodynamics.

The effect of alpha adrenergic block-ade on coronary blood flow regulation at rest was studied in 11 normally innervated patients and 8 cardiac allograft recipients by measuring arterial pressure and coronary sinus blood flow by thermodilution before and after alpha adrenergic blockade with phentolamine. Coronary vascular resistance was calculated by using coronary sinus blood flow and mean arterial pressure, and metabolic demand was estimated by the product of systolic arterial pressure and heart rate. In addition, the coronary sinus blood flow response to tachycardia was examined in 9 innervated patients and 12 denervated patients, with measurements repeated after phentolamine in 8 of the 9 innvervated patients and 6 of the 12 denervated patients. There was a 7.3+/-4.4% increase in coronary sinus blood flow in the innervated patients in response to alpha blockade, whereas the transplanted patients had an 8.2+/-1.8% fall in coronary sinus blood flow, despite equivalent changes in rate pressure product. The innervated patients also demonstrated a significantly greater increase in coronary sinus blood flow than did the transplanted patients during the first 5 s of an abrupt increase in heart rate (26+/-4 vs. 8+/-2.5 ml/min, P <0.001). This early response was blunted after alpha adrenergic blockade. We conclude that there is basal alpha adrenergic tone present on the coronary vasculature in man that is withdrawn by a sudden increase in heart rate.

Role of tachycardia as an inotropic stimulus in man.

We examined the inotropic effect of tachycardia in nine postsurgical aortocoronary bypass graft patients (with intact cardiac innervation) and nine cardiac allograft recipients (with denervated hearts). The changes in stroke volume (SV) and velocity of circumferential fiber shortening (VCF) which accompany sudden increases and decreases in atrial pacing frequency were determined by computer-aided fluoroscopic analysis of the motion of surgically implanted midwall myocardial markers. Because the first beat after a change in rate retains the frequency characteristics of the preceding rate, we compared the first posttachycardia beat with control beats and late tachycardia beats with the first tachycardia beat; afterload and preload for each pair of beats were similar. For an increase in heart rate of 50 beats/min, SV and VCF rose 79 and 64% from the first tachycardia beat to late tachycardia beats, and SV and VCF rose 8 and 35% from control beats to the first posttachycardia beat in the innervated group. Responses in the denervated group were not significantly different from those in the innervated group. The degree of the inotropic response was positively correlated with the magnitude of the increase in heart rate (r = 0.91). The decay in augmented contractility after decreasing the rate back to control levels fits an exponential relationship with a mean t((1/2)) of 1.7 s. Thus, in conscious man, increases in heart rate represent a positive inotropic stimulus, independent of other factors influencing ventricular performance and unaffected by neural innervation, and should be considered when changes in cardiac function are interpreted during serial studies or after drug administration.

Altered adrenergic activity in coronary arterial spasm: insight into mechanism based on study of coronary hemodynamics and the electrocardiogram.

To elucidate the pathophysiologic mechanism of coronary arterial spasm, the hypothesis was examined that underlying alterations in sympathetic activity may account for this syndrome in some patients. Observations were directed to alterations in coronary arterial hemodynamics and the electrocardiogram. Spasm of the left anterior descending coronary artery produced a mean increase in coronary vascular resistance of 107 percent (P less than 0.05) in four patients in whom coronary sinus blood flow was measured with the thermodilution technique. The alpha adrenergic blocking agent phentolamine, given intravenously, acutely reversed coronary spasm and its clinical manifestations in eight patients and reduced coronary resistance. In four patients, administration of the long-acting oral alpha blocking agent phenoxybenzamine (20 to 80 mg/day) caused disappearance of symptoms during a follow-up period of 3 to 12 months. Transient prolongation of the corrected Q-T interval preceded spontaneous or ergonovine maleate-provoked coronary spasm in 11 patients with variant angina pectoris, whereas no significant change in the Q-T interval followed ergonovine administration in 27 control patients with atypical chest pain who did not have coronary spasm. T wave inversions in the resting electrocardiogram were normalized by isoproterenol infusion in one patient and by long-term phenoxybenzamine treatment in four patients with variant angina pectoris. These Q-T and T wave changes are analogous to those described with unilateral or asymmetric stellate ganglion stimulation in animals. These observations suggest that alterations in the sympathetic nervous system that are consistent with asymmetric stellate ganglion activity and transient alpha adrenergic receptor stimulation can presage the development of coronary arterial spasm in some patients with variant angina pectoris.

Depressant effect of digoxin on atrioventricular conduction in man.

We examined the effect of chronically administered digoxin on atrioventricular (A-V) conduction in nine cardiac transplant recipients. We assessed A-V conduction by measuring the duration from the pacing stimulus to the onset of the QRS complex (S'R interval) and by determining the occurrence of Wenckebach periodicity during rapid atrial pacing. We made measurements during a control period and during a period of digoxin administration of up to 37 days. During the digoxin period, the cycle length at which Wenckebach block occurred was prolonged by 14% of the control value and the S'R interval was significantly prolonged at paced rates of 110 beats per minute and faster. After digoxin was discontinued, the Wenckebach periodicity and S'R interval returned to control values. Atropine and propranolol did not alter digoxin's effect on A-V conduction. We conclude that digoxin exerts a direct (or non-neurally mediated) depressant effect upon A-V conduction in man, although the stress of tachycardia is necessary to demonstrate the effect.

Reduction of coronary blood flow during coronary artery spasm occurring spontaneously and after provocation by ergonovine maleate.

A 50-year-old man suffering from recurrent chest pain accompanied by transient ST-segment elevation developed spasm of the left anterior descending coronary artery after receiving ergonovine maleate. During spontaneous chest pain, thermodilution coronary sinus blood flow fell from 96 ml/min to 46 ml/min, while the coronary sinsu arteriovenous oxygen difference widened from 9.82 volumes percent to 11.3 volumes percent. During spontaneous relief of pain, coincident with resolution of the ST-segment changes, coronary sinus blood flow gradually rose to 135 ml/min, while coronary sinus arteriovenous oxygen difference narrowed to 6.82 volumes percent. Similar aterations in coronoary sinus blood flow accompanied chest pain provoked by ergonovine maleate. A thallium-201 scan confirmed a perfusion defect in the distribution the left anterior descending coronary artery. Thus, coronary artery spasm can produce a marked deficity in coronary blood flow that is associated with increased myocardial oxygen extraction; release of spasm creates a hyperemic response.

Traumatic pulmonary artery--left atrial fistula: an unusual case of cyanosis in an adult.

Eighteen months after sustaining a stab wound to the left upper chest, a 59-year-old man presented with cyanosis and extertional dyspnea. Arterial desaturation due to a central 22 per cent right-to-left shunt was present. A selective pulmonary arteriogram demonstrated a fistula between the main pulmonary artery and the left atrium. At operation the fistula was closed. A laceration of the pulmonic valve and healed pericarditis were present. Marked symptomatic improvement followed the operation, but a murmur of pulmonic valvular regurgitation persisted. The fistula and laceration of the pulmonic valve were probably traumatic in origin.

The effects of ergonovine maleate on coronary arterial size.

Changes in coronary arterial size due to ergonovine maleate are described and quantitated in 90 patients--18 with typical angina pectoris, 56 with atypical chest pain, nine with variant angina pectoris, and seven heart transplant (allograft) recipients. We observed two angiographic changes in the diameter of coronary arteries: 1) spasm, which was characterized by occlusion or marked (greater than 85%) focal or diffuse vessel narrowing, or 2) relatively mild and diffuse vessel narrowing, which was interpreted as the normal pharmacologic response to the drug. Serial bolus injections of 0.05 mg, 0.10 mg and 0.25 mg of ergonovine maleate produced diffuse narrowing of the diameter of coronary arteries of 10 +/- 1.5%, 16 +/- 1.4% and 20 +/- 1.3% (mean +/- SEM), respectively, in the 72 patients with anginal syndromes who did not develop coronary spasm. The degree of coronary arterial narrowing was the same in heart transplant recipients and in patients with normally innervated hearts who did not develop coronary spasm. We believe the normal pharmacologic response to ergonovine maleate was due to a direct vasoconstrictor action of the drug; this action was independent of neural control extrinsic to the heart.