Extracellular ATP induces fast and transient non-selective cationic currents and cytosolic Ca2+ changes in human umbilical artery smooth muscle cells.

Ionotropic purinergic receptors (P2X) are expressed in endothelial and smooth muscle cells of blood vessels. ATP acting on smooth muscle P2X receptors is able to induce vasoconstriction in different kind of vessels. However, to our knowledge, there are no reports that directly show the activity of these purinergic receptors in native human vascular smooth muscle cells. In this work, we describe for the first time an ATP-induced current in freshly isolated human umbilical artery (HUA) smooth muscle cells. The current was measured by patch-clamp technique in whole-cell condition on cells clamped at -50 mV. At 100 µM of ATP the current showed a rapid activation and desensitization, and was carried by both Na(+) and Ca(2+). The current was completely blocked by suramin (300 µM) and partially blocked by 100 µM of Zn(2+) without affecting the kinetic of desensitization. All these properties suggest that the ATP-induced ionic currents are mediated through P2X(1)-like receptors. Moreover, we show that ATP transiently increased cytosolic Ca(2+) in "in situ" smooth muscle cells of intact HUA segments and that this response is dependent of extracellular and intracellular Ca(2+). These data expand the knowledge of purinergic receptors properties in vascular smooth muscle cells and the probable role of ATP as a paracrine modulator of contractile tone in a human artery which is fundamental for feto-placental blood flow.

Reversal of left ventricular intracavitary gradient with intracavitary diastolic regurgitation in hypertrophic obstructive cardiomyopathy.

A 73 year old man presented with angina and nonsustained ventricular tachycardia. Cardiac catheterization revealed the dynamic systolic intracavitary gradient of hypertrophic obstructive cardiomyopathy. Abnormal isovolumetric relaxation resulted in the development of a diastolic gradient from the left ventricular outflow tract to the left ventricular apex accompanied by intracavitary regurgitation of contrast material from the outflow tract to the left ventricular body during left ventriculography. This case provides hemodynamic and angiographic confirmation of abnormal isovolumetric relaxation in this syndrome and insight into its mechanism.

Procainamide pharmacokinetics in patients with acute myocardial infarction or congestive heart failure.

Abnormal procainamide pharmacokinetics (prolonged half-life and decreased volume of distribution) and pharmacodynamics (decreased threshold for the suppression of premature ventricular complexes) have been suggested in patients with acute myocardial infarction or congestive heart failure, or both. To better define procainamide kinetics, 37 patients in the acute care setting received intravenous procainamide (25 mg/min, median dose 750 mg) with peak and hourly blood samples taken over 6 hours. Compared with the 10 control patients, the 12 patients with acute myocardial infarction and the 15 patients with congestive heart failure had normal procainamide pharmacokinetics with respect to half-life (2.3 +/- 1.0, 2.5 +/- 0.9 and 2.6 +/- 0.8 hours, respectively), volume of distribution (1.9 +/- 0.7, 1.8 +/- 0.4 and 1.8 +/- 0.5 liters/kg, respectively), clearance (11.3 +/- 7.5, 9.3 +/- 3.6 and 9.1 +/- 3.5 ml/min per kg, respectively) and unbound drug fraction (66 +/- 9, 66 +/- 9 and 69 +/- 4%, respectively). Low thresholds for greater than 85% premature ventricular complex suppression were confirmed in these patients (median 4.7 micrograms/ml in patients with acute myocardial infarction and 3.3 micrograms/ml in patients with congestive heart failure). Thus, differences in the response of premature ventricular complexes to procainamide reflect electropharmacologic differences dependent on clinical setting rather than pharmacokinetic abnormalities. Furthermore, the reduction of procainamide dosing in patients with acute myocardial infarction or congestive heart failure, based solely on prior kinetic data, may result in inappropriate antiarrhythmic therapy.

Cardiac arrhythmias associated with prophylactic pacing during coronary angiography.

Data from 518 consecutive cardiac catheterizations were analyzed to test the value of prophylactic pacemaker insertion during coronary angiography and to compare the incidence of arrhythmic complications in patients with and without pacemakers. In patients without pacing (n = 273), 1 episode of ventricular fibrillation occurred, which responded promptly to defibrillation. Sinus bradycardia (fewer than 30 beats/min for 10 seconds) was recorded in 74 patients (27%) and required treatment in 30 (11%). No patient required or would have benefited from pacemaker placement. Of the 245 patients with prophylactic pacemakers, there was an increased incidence of all ventricular (9 vs 1; p less than 0.013) and supraventricular (5 vs 0; p less than 0.046) arrhythmias. Pacemaker-associated induction of ventricular fibrillation occurred in 2 patients and was clearly related to electrical stimulation during a normally non-vulnerable period of the cardiac cycle. In conclusion, routine prophylactic pacemaker insertion during coronary angiography is not warranted in patients with normal sinus rhythm and normal atrioventricular conduction. More information is needed to determine if pacing is needed in patients with conduction system disease.

Cardiovascular findings in quadriplegic and paraplegic patients and in normal subjects.

Seven normal, 7 paraplegic and 7 quadriplegic patients underwent cross-sectional cardiovascular evaluation, including recording of sitting heart rate, blood pressure and echocardiography. Quadriplegic patients had a 26% lower left ventricular (LV) mass index (75 +/- 13 g/m2, p less than 0.01) compared with normal volunteers (102 +/- 16 g/m2) or paraplegic patients (110 +/- 26 g/m2). Six quadriplegic patients and 3 paraplegic patients had an unusual pattern of LV posterior wall asynergy, which was associated with a significant rightward shift of the frontal-plane QRS axis (92 +/- 22 degrees vs 42 +/- 41 degrees, p less than 0.005) and smaller left atrial dimensions (2.4 +/- 0.4 vs 3.0 +/- 0.3 cm, p less than 0.005). The quadriplegic group was characterized by a significantly reduced mean blood pressure (67 +/- 7 vs 88 +/- 8 mm Hg in normal subjects, p less than 0.002), high normal peripheral resistances (22 +/- 5 vs 17 +/- 5 units in normal subjects, difference not significant) and a markedly reduced calculated cardiac output (3.2 +/- 0.6 vs 5.4 +/- 1.4 liters/min in normal subjects, p less than 0.01). Hemodynamic data for the paraplegic patients were similar to those in the normal group. A decrease in LV wall stress, mediated primarily by a decrease in venous return, appeared to result in the "adaptive" cardiac atrophy seen in these quadriplegic patients. LV asynergy was common and also may be related to a decrease in cardiac filling.

Anomalous separate origin of the septal perforator coronary artery from the left sinus of valsalva.

The anomalous separate origin of the first septal perforator from the left sinus of Valsalva is described. Previously documented anomalous origins of the septal perforator include the left main coronary artery, the right coronary artery, the right sinus of Valsalva, a diagonal coronary artery, the circumflex coronary artery, and its obtuse marginal branch. We could not find any previous description of the septal perforator originating from a separate ostium in the left sinus of Valsalva.

Angiographic demonstration of atherosclerotic stenosis, arterial spasm, and thrombus formation in an infarct-related coronary artery.

Clinical, angiographic, and pathologic data support the contention that atherosclerosis, platelet aggregation, and coronary vasomotility work in unison to cause coronary thrombosis, which in turn leads to myocardial infarction. A patient is described in whom, 2 months after an acute myocardial infarction, inducible coronary artery spasm and a nonocclusive thrombus were angiographically demonstrated at the site of a minimal atherosclerotic narrowing in the infarction-related vessel. This report, to the best of our knowledge, is the first time that these three pathophysiologic mechanisms have been shown, in vivo, to be occurring concomitantly in an infarct-related vessel. Documentation of the unified occurrence of these phenomena support the current concept of the pathophysiology of myocardial infarction.

Combined vasodilator and inotropic therapy of heart failure: experimental and clinical concepts.

Vasodilators facilitate ventricular emptying by affording earlier onset of left ventricular (LV) ejection and increased stroke volume with achievement of a reduced end-systolic pressure and volume. Agents with positive inotropic properties increase stroke volume by shifting the end-systolic pressure-volume curve to the left through augmented force and velocity of contraction. With impedence reduction, improvement in pump performance occurs concomitant with reduced cardiac energy requirements (MVO2); positive inotropic agents most circumstances increase MVO2. The combination of a vasodilator and positive inotropic agent, as opposed to either alone, in the conscious animal shifts to the left and increases the slope of the LV end-systolic pressure-volume relation. Cardiac efficiency, defined by the slope of the relation between stroke volume and systolic tension, is increased by the combination of the drugs. In clinical heart failure, nitroprusside alone lowers LV preload with a modest increase in cardiac output (CO); dopamine markedly increases CO with little fall in LV preload. In combination the two agents achieve the individual beneficial effects of each drug, and cardiac efficiency indices are improved. Thus combined vasodilator and inotropic therapy appears to have a sound physiologic rationale and clinically documented beneficial effect superior to either modality alone.