Search PubMed⌕ Search

Biomedical subjects

P Ganz

Publications and source records attributed to P Ganz.

At least 145 records · Page 8Linked to original sources
PubMed1987

Angiotensin II stimulation of vascular smooth muscle phosphoinositide metabolism. State of the art lecture.

Phosphoinositide hydrolysis is an integral step in the activation of vascular smooth muscle by angiotensin II. Sequential phospholipase C-mediated hydrolysis of the polyphosphoinositides and phosphatidylinositol in cultured vascular smooth muscle cells stimulated with angiotensin II results in a coordinated series of biochemical events: a transient formation of inositol trisphosphate associated with calcium mobilization, and a biphasic, sustained formation of diacylglycerol associated with activation of protein kinase C and cytosolic alkalinization. The initial, rapid phase and the sustained phase of the angiotensin II response appear to be differentially controlled. Formation of inositol trisphosphate and mobilization of calcium are attenuated by activation of protein kinase C. Sustained diacylglycerol formation is promoted by cytosolic alkalinization, and appears to require cellular processing of the angiotensin II-receptor complex. Calcium and cyclic guanosine 3',5'-monophosphate do not appear to regulate phospholipase C-mediated phosphoinositide hydrolysis in vascular smooth muscle. Thus, regulation of angiotensin II-stimulated second messenger generation in vascular smooth muscle is complex, perhaps involving protein kinase C activation, changes in intracellular pH, and processing of the angiotensin II-receptor complex.

Angiotensin II↗
PubMed1986

Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries.

Acetylcholine is believed to dilate normal blood vessels by promoting the release of a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). By contrast, if the endothelium is removed experimentally, acetylcholine constricts blood vessels. We tested the hypothesis that muscarinic cholinergic vasodilation is impaired in coronary atherosclerosis. Graded concentrations of acetylcholine and, for comparison, the nonendothelial-dependent vasodilator nitroglycerin were infused into the left anterior descending artery of eight patients with advanced coronary stenoses (greater than 50 percent narrowing), four subjects with angiographically normal coronary arteries, and six patients with mild coronary atherosclerosis (less than 20 percent narrowing). Vascular responses were evaluated by quantitative angiography. In several segments each of four normal coronary arteries, acetylcholine caused a dose-dependent dilation from a control diameter of 1.94 +/- 0.16 mm to 2.16 +/- 0.15 mm with the maximal acetylcholine dose (P less than 0.01). In contrast, all eight of the arteries with advanced stenoses showed dose-dependent constriction, from 1.05 +/- 0.05 to 0.32 +/- 0.16 mm at the highest concentration of acetylcholine (P less than 0.01), with temporary occlusion in five. Five of six vessels with minimal disease also constricted in response to acetylcholine. All vessels dilated in response to nitroglycerin, however. We conclude that paradoxical vasoconstriction induced by acetylcholine occurs early as well as late in the course of coronary atherosclerosis. Our preliminary findings suggest that the abnormal vascular response to acetylcholine may represent a defect in endothelial vasodilator function, and may be important in the pathogenesis of coronary vasospasm.

Acetylcholine↗
PubMed1986

Role of reflex sympathetic withdrawal in the hemodynamic response to an increased inotropic state in patients with severe heart failure.

Newer positive inotropic agents used in the treatment of severe heart failure not only increase cardiac contractility, but also cause peripheral vasodilation. It is not known to what extent this vasodilation is due to a direct peripheral action of the drug, as opposed to reflex withdrawal of sympathetic tone secondary to an augmented inotropic state. In 16 patients with severe heart failure, a 48 hour intravenous infusion of milrinone, a positive inotropic vasodilator drug, resulted in an increase in stroke volume index from 26 +/- 2 to 34 +/- 3 ml/m2 (p less than 0.001), a reduction in forearm vascular resistance measured by venous plethysmography from 43 +/- 5 to 27 +/- 3 U (p less than 0.003) and an increase in forearm venous capacitance from 2.1 +/- 0.2 to 2.9 +/- 0.2 ml/100 ml (p less than 0.001). To determine whether a withdrawal of sympathetic tone contributed to this vasodilation, milrinone was infused directly into the left main coronary artery in eight of the patients, thereby eliminating any direct vascular effects of the drug. Intracoronary milrinone (50 micrograms/min) caused an increase in peak positive first derivative of pressure (658 +/- 49 to 784 +/- 68 mm Hg/s; p less than 0.01) and stroke volume index (20 +/- 2 to 25 +/- 3 ml/m2; p less than 0.0001), which was associated with a reduction in plasma norepinephrine from 540 +/- 101 to 423 +/- 90 pg/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Administration Schedule↗
PubMed1986

Short- and long-term interactions of endothelium and vascular smooth muscle in coculture: effects on cyclic GMP production.

In intact blood vessels, many vasodilators act by stimulating the release from endothelium of factor(s) that relax vascular smooth muscle and stimulate increases in cGMP. To investigate how endothelium regulates cGMP production in vascular smooth muscle, bovine aortic endothelial cells and rat aortic smooth muscle cells were cultured both separately and together in cocultures for 48 hr. Nitroprusside (1 mM) increased intracellular cGMP concentration 30-fold in smooth muscle cells (from a basal level of 103 +/- 54 fmol/mg of cell protein to 2920 +/- 1800 fmol/mg) but only 2-fold in endothelial cells (from 41 +/- 7 fmol/mg to 93 +/- 23 fmol/mg). When endothelial and smooth muscle cells were cocultured as a mixed cell population (1:1 cell ratio), both basal and nitroprusside-stimulated cGMP levels were significantly increased (550 +/- 250 and 13,240 +/- 9950 fmol/mg of total cell protein, respectively). The calcium ionophore A23187 (10 microM) caused no increase in cGMP concentration in either cell type cultured alone but produced a 6-fold increase in cocultures. Neither aspirin nor 5,8,11,14-icosatetraynoic acid influenced these results. No changes in cAMP levels were detected. Using cocultures in which one cell type was grown on microcarrier beads, we have shown that cGMP increased only in vascular smooth muscle cells and was not dependent upon the formation of junctions between endothelium and smooth muscle cells. In long-term (48-hr) mixed-cell cocultures, but not in short-term microcarrier cocultures, amplification of the nitroprusside-induced increase in cGMP was observed. These results show that responses associated with endothelium-dependent relaxation can be reconstituted in cultured endothelial and vascular smooth muscle cells and that endothelium generates a humoral factor(s) that stimulates accumulation of smooth muscle cGMP and has a longer-term effect that amplifies guanylate cyclase stimulation by nitroprusside, a drug acting directly upon smooth muscle to stimulate formation of the cyclic nucleotide. Cultured cells provide a valuable model system for the study of endothelium-vascular smooth muscle interactions.

Animals↗
PubMed1986

Side branch occlusion complicating percutaneous transluminal coronary angioplasty.

A frequent concern during angioplasty is the possibility of occluding important side branches that originate in arterial stenoses subjected to balloon dilatation. The effect of dilatation on 93 side branches (greater than or equal to 1 mm in diameter) was evaluated in 86 patients undergoing percutaneous transluminal coronary angioplasty (PTCA) in whom those branches arose directly in dilated segments of the left anterior descending, circumflex, or right coronary arteries. Seventy-six of the 93 side branches had minor (less than 50%) narrowing at their origin. Among these side branches, nine (12%) were compromised by PTCA. Seventeen of the 93 side branches had greater than 50% ostial stenosis. Significantly more of these side branches (seven of seventeen, or 41%) were compromised by PTCA (P less than .01). Even when compromise does occur, it usually takes the form of increased stenosis rather than total occlusion. The presence of side branches originating in stenotic lesions is not a contraindication to PTCA since serious compromise of such branches rarely results from this procedure.

Angioplasty, Balloon↗
PubMed1986

Vasoactive intestinal peptide: vasodilatation and cyclic AMP generation.

Vasoactive intestinal peptide (VIP) is a putative neurotransmitter that causes vasodilation when injected intravenously. To learn more about the vasodilator actions of VIP, studies were performed on the rat mesenteric arterial bed and on cultured smooth muscle cells derived from both the rat mesenteric artery and aorta. In isolated perfused rat mesenteric artery beds, VIP caused relaxation at the threshold concentration of less than 1 nM and a maximal fall in perfusion pressure similar to that obtained with isoproterenol. VIP stimulated adenylate cyclase in cultured vascular smooth muscle cells in a concentration range of 10(-10)-10(-6) M; maximum activity was increased 2.7 +/- 0.6- and 3.4 +/- 0.4-fold above basal in mesenteric and aortic smooth muscle cells, respectively. The threshold and the half-maximal concentrations of VIP for adenylate cyclase stimulation were more than 50-fold lower than those for both prostaglandin E1 and isoproterenol in cultured mesenteric and aortic cells. Similar effects on cyclic AMP generation in response to VIP were observed in isolated rat mesenteric artery rings. Immunocytochemical examination of the rat mesenteric artery bed in situ demonstrated dense innervation of small- and medium-size vessels with nerve fibers containing VIP-like immunoreactivity. Thus VIP is present in the rat mesenteric artery, a peripheral arterial bed, and is a potent vasodilator that can activate vascular smooth muscle adenylate cyclase and thus potentially contribute to the regulation of vascular tone.

Adenylyl Cyclases↗
PubMed1986

Separation of the direct myocardial and vasodilator actions of milrinone administered by an intracoronary infusion technique.

To determine the relative contributions of milrinone's positive inotropic and vasodilator actions in patients with severe congestive heart failure, the drug was administered by constant infusion directly into the left main coronary artery of 11 patients with New York Heart Association functional class III or IV heart failure. Intracoronary infusion of milrinone at rates up to 50 micrograms/min had no effect on mean arterial pressure or systemic vascular resistance but resulted in dose-related increases in peak positive dP/dt (+21%), stroke volume index (+18%), and stroke work index (+21%) and decreases in heart rate (-3%), mean right atrial pressure (-25%), and left ventricular end-diastolic pressure (-17%). In eight patients, intravenous administration (75 micrograms/kg) after the intracoronary infusion resulted in significant decreases in mean arterial pressure (-14%) and systemic vascular resistance (-40%), further increase in stroke volume index compared with intracoronary administration, and further decreases in mean right atrial and left ventricular end-diastolic pressures compared with intracoronary administration. These data indicate that milrinone exerts both positive inotropic and vasodilator actions that contribute significantly to the drug's overall hemodynamic effect.

Adult↗
PubMed1986

Value of the intracoronary electrocardiogram to monitor myocardial ischemia during percutaneous transluminal coronary angioplasty.

To enhance detection of ischemia during percutaneous transluminal coronary angioplasty (PTCA), unipolar intracoronary electrocardiograms (ECGs) were recorded during PTCA in 25 patients from the tips of guidewires positioned distal to stenoses being dilated. Surface electrocardiographic leads chosen to reflect likely areas of reversible ischemia during PTCA were recorded simultaneously. In 21 of 29 stenoses dilated (72%), ST segment elevation and/or T wave peaking in intracoronary ECG appeared during balloon inflation and disappeared after deflation, accompanied by transient angina on 19 occasions. Two patients had transient ST segment elevation in intracoronary ECGs during PTCA without associated angina. ST changes in the surface ECG during PTCA were seen on only nine occasions (31%), always accompanied by ST segment elevation in the intracoronary ECG that appeared earlier and was of much greater magnitude. Five patients with prior myocardial infarction and aneurysm formation had fixed ST segment elevation in the intracoronary ECG unrelated to balloon inflation. Myocardial ischemia during PTCA can be detected easily with intracoronary ECGs and with greater sensitivity than that of the surface ECG. Furthermore, intracoronary ECGs may help to clarify the nature of chest pain during balloon inflation or during suspected complications.

Adult↗
PubMed1985

New insights into the cellular mechanisms of vasospasm.

Previous attempts to define the etiology of coronary artery spasm have focused on such mechanisms as autonomic nervous system dysfunction or enhanced platelet activation leading to high levels of circulating vasoconstrictors. More recent evidence, however, suggests that the basic abnormality may be hypercontractility of the arterial wall associated with the atherosclerotic process itself. Results of both animal experiments and clinical studies support a role for certain cellular events in atherogenesis, including endothelial injury, presence of mitogenic factors and leukotrienes generated by platelets and macrophages, changes in histamine and serotonin receptor density of vascular smooth muscle and neovascularization of atherosclerotic plaque. The mechanisms postulated to underlie coronary vasospasm are discussed, relative to the clinical characteristics of vasospastic angina and the possible therapeutic implications.

Animals↗
PubMed1985

Addition of nifedipine to maximal beta-blocker-nitrate therapy: effects on exercise capacity and global left ventricular performance at rest and during exercise.

Nifedipine is a potent coronary vasodilator in the resting state and an effective afterload-reducing agent. This study was undertaken because of the concern that the addition of nifedipine to beta-blocker therapy could produce serious untoward hemodynamic consequences. Although this combination is usually well tolerated, occasional reports suggest that the combination of nifedipine and beta-blocking agents may increase the likelihood of congestive heart failure, severe hypotension or exacerbation of angina. Further, there is a need to know if the addition of nifedipine to therapy with maximally tolerated doses of long-acting nitrates and beta blockers would provide further symptomatic relief without excessive adverse effects. Finally, the effect of adjunctive nifedipine on global left ventricular performance at rest and during exercise was examined. Sixteen patients, all of whom had 3 or more episodes per week of angina pectoris despite therapy with long-acting nitrates and beta blockers, were selected. Radionuclide ventriculography was performed at rest and during exercise; global ejection fractions (EFs) were determined by manually tracing the left ventricular end-diastolic perimeter with an electronic cursor. In the first phase, beta blockers and nitrates were used; in the second phase nifedipine, 10 mg every 6 hours, was added and titrated to reduce systolic blood pressure at rest by at least 10 mm Hg or until intolerable adverse effects occurred. When nifedipine was added to therapy, the difference between global EF at rest and during exercise was reduced from - 0.15 to + 0.02 (p less than 0.00001); exercise duration was increased from 431 seconds to 532 (p less than 0.001), with only 8 patients limited by angina, compared with 16 during the initial therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Usefulness of transstenotic coronary pressure gradient measurements during diagnostic catheterization.

A difficult problem in coronary arteriography is the assessment of the hemodynamic significance of stenoses that appear angiographically to be of only moderate severity (25 to 75% diameter narrowing). This is particularly important in patients who may be candidates for invasive therapy, such as percutaneous transluminal coronary angioplasty (PTCA) or coronary bypass surgery. To determine the significance of such lesions, we measured transstenotic coronary pressure gradients in 15 patients with angiographically moderate stenoses. For comparison, similar measurements were made in 17 patients with severe stenoses (more than 75% diameter narrowing) being considered for PTCA. The transstenotic pressure gradients were measured with a 2.0Fr polyvinyl chloride catheter cleared of microbubbles of air by flushing with carbon dioxide and degassed saline solution and attached to a low-volume displacement transducer for optimal frequency response. Mean transstenotic pressure gradients greater than 10 mm Hg at rest or more than 20 mm Hg under conditions of high coronary blood flow, as induced by Renografin 76, appeared to be associated with objective evidence of myocardial ischemia and symptomatic relief from PTCA. Smaller pressure gradients occurred in patients whose symptoms probably were not ischemic in nature. Transstenotic pressure gradient determination performed at the time of diagnostic catheterization may provide assistance in clinical decision-making in selected patients with angiographically moderate stenoses.

Angioplasty, Balloon↗
PubMed1985

Attenuation of coronary vascular resistance by selective alpha 1-adrenergic blockade in patients with coronary artery disease.

Alpha-adrenergic-mediated coronary vasoconstriction during stress such as cold pressor testing may contribute to myocardial ischemia by increasing coronary vascular resistance in patients with severe coronary artery disease. Nonselective alpha-receptor blockade with phentolamine abolishes both the peripheral and coronary vasoconstriction during cold pressor testing, but causes reflex tachycardia and increased inotropy. To determine the role of selective alpha 1-receptor blockade, the changes in coronary vascular resistance during cold pressor testing were measured in 18 patients with coronary artery disease before and after intravenous administration of 100 mg of trimazosin. Cold pressor testing was performed at a constant paced subanginal heart rate of 95 +/- 5 beats/min (+/- 1 SD). Before trimazosin, cold pressor testing increased mean arterial pressure by 9 +/- 4% (102 +/- 14 to 111 +/- 14 mm Hg, p less than 0.001) with no change in coronary sinus blood flow, but significantly increased coronary vascular resistance by 15 +/- 19% (1.02 +/- 0.46 to 1.15 +/- 0.57 units, p less than 0.05). Five minutes after trimazosin, cold pressor testing increased mean arterial pressure by 6 +/- 5% (p less than 0.001) with a marked attenuation of the increase in coronary vascular resistance (6 +/- 11%, p = NS), which was significantly less than before trimazosin (p less than 0.02). Trimazosin did not increase plasma norepinephrine concentration at rest, suggesting that in the dosage used trimazosin caused selective alpha 1-receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1985

Percutaneous transluminal coronary angioplasty with an over-the-wire system.

The original Gruentzig coaxial catheter system for percutaneous transluminal coronary angioplasty (PTCA) utilized a blunt, closed-end, inner balloon catheter with a short guide wire attached to its tip. Options for safely crossing severe stenoses with this large, nonmaneuverable catheter were limited. More recently, over-the-wire systems have been developed in which the lesion initially is crossed with a small-caliber floppy or steerable guide wire, then by the balloon catheter advanced over the wire. Technical success was achieved in 78 of our first 100 PTCAs with this system. Significant cardiac complications occurred in ten patients, seven of whom required emergency coronary bypass surgery. A recently published survey of all PTCA techniques reported a technical success rate of 62%. Our higher success rate may be attributed to certain advantages of the over-the-wire system, which are discussed in detail. A learning curve is associated with this procedure: our success rate was 65% in the first 20 cases but 81% thereafter. These results can be considered typical of those expected at hospitals now beginning PTCA programs with advanced over-the-wire technology.

Angioplasty, Balloon↗
PubMed1985

Reversible microcarrier-mediated junctional communication between endothelial and smooth muscle cell monolayers: an in vitro model of vascular cell interactions.

Junctional communication between cultured monolayers of aortic endothelial and smooth muscle cells was established as an in vitro model of vessel wall cell interactions. Confluent monolayers of endothelial cells on microcarriers placed on the surface of a smooth muscle cell monolayer became attached within 1 hour. After 3 hours of contact co-culture, approximately 4% of each monolayer was involved in heterocellular attachment (range 2% to 6%; 4 to 12 cells per microcarrier). Endothelial-smooth muscle cell junctions formed between the two cell populations at the sites of attachment on the lower surface of each microcarrier. When either endothelial cells or smooth muscle cells were prelabeled with [3H]uridine, intracellular nucleotide was rapidly transferred across the region of heterocellular attachment to the complementary cell population. Heterocellular gap junctional transfer was inhibited when endothelial-smooth muscle attachment was prevented by slowly rocking the culture vessel. No evidence of nucleotide transfer was obtained when endothelial cells were co-cultured with MDCK cells incapable of forming gap junctions. Contact co-culture of endothelium and smooth muscle cells were reversed by gentle agitation of the cultures; the microcarriers detached allowing the recovery of pure cell populations. The contact co-culture technique is well suited to studies of vascular cell interactions and is of general applicability to anchorage dependent cells.

Animals↗
PubMed1984

Combination therapy with ibuprofen and methadone for chronic cancer pain.

This randomized double-blind crossover study compares the narcotic methadone alone with methadone in combination with the peripherally acting, antiprostaglandin agent ibuprofen (Motrin, Upjohn) in 28 patients with moderate to severe cancer-related pain, who were already using a narcotic for pain relief. Results show that the addition of 600 mg of ibuprofen to either 2.5 or 5 mg of methadone significantly increased analgesia, without concomitantly increasing side effects or euphoria.

Adult↗