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Biomedical subjects

R Bolli

Publications and source records attributed to R Bolli.

At least 181 records · Page 10Linked to original sources
PubMed1984

Intravascular microaggregation and in vitro platelet aggregation in coronary artery disease.

To investigate in vivo and in vitro microaggregation in coronary artery disease, we obtained blood samples from the coronary sinus (CS), pulmonary artery (PA), and aorta (AO) in patients undergoing cardiac catheterization. An electronic particle size analyzer was used to quantify microaggregates 13 to 81 mu in diameter in blood. In the first group of 58 patients, preformed circulating microaggregates and platelet responsiveness to ADP were assessed in AO and PA blood only. The coronary artery disease patients did not have significantly higher volumes of preformed in vivo aggregates in either AO or PA blood. However, the mean aggregate size in response to 0.2 microM ADP in vitro was larger in both AO and PA blood in patients with coronary disease [12.4 +/- 0.9 vs. 9.4 +/- 1.4 X 10(3) mu3 (AO); 12.5 +/- 0.9 vs. 8.3 +/- 0.7 0.7 X 10(3) mu3 (PA)]. In a second group of 46 patients, CS, AO and PA samples were compared using the same methods. The volume of microaggregates preformed in vivo was significantly greater in CS blood than in PA or AO blood in patients with and without coronary disease. The volume and mean size of aggregates induced by ADP in vitro were smaller in CS blood compared to PA. In conclusion, the volume of in vivo microaggregates is increased in CS blood, independent of coronary disease, but significant volumes are not found in PA or AO blood. Patients with coronary disease have more reactive platelets to in vitro aggregatory agents in AO and PA samples of similar hematocrit.

Adenosine Diphosphate↗
PubMed1984

Gonococcal endocarditis: a case series demonstrating modern presentation of an old disease.

Gonococcal endocarditis appeared with striking frequency in the preantibiotic era compared with its surprising rarity today. We present a series of four episodes of gonococcal endocarditis, which presented to our institution in the last 2 years, after no cases in the previous decade. Three episodes involved the aortic valve and required emergency aortic valve replacement. One episode involved the tricuspid valve and was successfully cured with antibiotic infusion alone. Combining our four patients with the available 25 well-documented gonococcal endocarditis cases reported in the English medical literature during the antibiotic era, we demonstrated that the disease incidence may be increasing, that infections more often involve left-sided cardiac structures (particularly the aortic valve), and that the association with a quotidian fever curve, rash and arthritis, and overt gonococcal infection is less common than previously reported. These patients frequently present with fulminant and dramatic valvular insufficiency without immediately positive blood cultures and complete echocardiographic evaluation seems to provide a valuable aid in making a presumptive diagnosis of endocarditis and directing appropriate clinical management.

Adult↗
PubMed1984

Effect of alpha-adrenergic blockade on arrhythmias induced by acute myocardial ischemia and reperfusion in the dog.

Studies in cats suggest alpha-adrenergic contributions to arrhythmias during myocardial ischemia and reperfusion. The validity of this concept in other species, however, remains uncertain. Thus, 106 chloralose-anesthetized open-chest dogs undergoing a 25 min coronary artery occlusion followed by reperfusion received saline (n = 52), prazosin (1 mg/kg, n = 26), phentolamine (5 mg/kg, n = 18), or phentolamine (same dose) + propranolol (1 mg/kg, n = 10). Alpha-blockade was confirmed by alpha-agonist dose-response studies. In phentolamine-treated dogs, arterial pressure and heart rate were kept constant to prevent exacerbation of ischemia. Control and treated groups were comparable with respect to variables known to affect arrhythmias, such as size of occluded and reperfused vascular beds, coronary collateral flow, severity of ischemia estimated from intramyocardial CO2 tension, and peak reactive hyperemia. During coronary occlusion, the number of single premature ventricular complexes was reduced by phentolamine (P less than 0.01), but not by prazosin or phentolamine + propranolol; no treatment affected the total number of couplets, ventricular tachycardia episodes and ventricular ectopic complexes, or the incidence of ventricular tachycardia and ventricular fibrillation. During coronary reperfusion, arrhythmias did not differ in control and treated groups. Thus, selective alpha 1-(prazosin), nonselective alpha 1- and alpha 2-(phentolamine), and combined alpha- and beta-blockade (phentolamine + propranolol) failed to attenuate complex arrhythmias induced by acute myocardial ischemia and reperfusion. Alpha-adrenergic mechanisms appear unimportant in the genesis of these arrhythmias in the canine model.

Adrenergic alpha-Antagonists↗
PubMed1984

Influence of acute arterial hypertension on myocardial infarct size in dogs without left ventricular hypertrophy.

During acute myocardial infarction an increase in arterial pressure is common in patients who were previously normotensive and, therefore, do not have left ventricular hypertrophy. However, the effect of hypertension on infarct size in the absence of hypertrophy is uncertain. Thus, 32 open chest dogs underwent a 2 hour occlusion of the mid-left anterior descending coronary artery followed by 3 hours of reperfusion. Immediately after occlusion, 14 dogs were randomized to a hypertension group (intravenous phenylephrine infusion starting 5 minutes after occlusion and terminating at the time of reperfusion, with heart rate kept constant by atrial pacing) and 18 dogs to a control group (equivalent volumes of saline solution intravenously). Twelve of the 32 dogs were excluded from analysis because they developed ventricular fibrillation during coronary occlusion or reperfusion. In the hypertension group (n = 10), the mean arterial pressure increased significantly within 10 minutes of coronary occlusion (146 +/- 7 versus 109 +/- 11 mm Hg in 10 control dogs, p less than 0.01) and was maintained approximately 40 mm Hg higher than in the control group (p less than 0.01) throughout the ischemic period. Heart rate was similar in the two groups throughout the experiment. After the dogs were sacrificed, the region normally supplied by the occluded artery (anatomic "region at risk") was identified by simultaneous perfusion of the aortic root and the coronary artery distal to the occlusion. The heart was sectioned transversely and stained with triphenyltetrazolium-chloride. The infarcted area and the anatomic risk area were determined by video planimetry.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Platelet-mediated thrombosis in stenosed canine coronary arteries: inhibition by nicergoline, a platelet-active alpha-adrenergic antagonist.

The effects of nicergoline, a new agent that blocks alpha-adrenergic receptors and inhibits platelet phospholipase, were evaluated in a canine model of platelet-mediated coronary thrombosis. In 48 open chest dogs, the circumflex coronary artery was stenosed by plicating the artery wall with a suture. Thirty-four of the 48 dogs exhibited cyclic reductions in flow in the stenotic vessel, followed by a sudden return to control levels. The reductions in flow were unabated in all but two dogs after heparin administration (1,000 U/kg per h), unaffected by large doses of nitroglycerin and nifedipine and associated with platelet aggregates in the stenotic segment (demonstrated by histologic and electron microscopic examination). These observations support the conclusion that the flow reductions were caused by platelet aggregation rather than by fibrin deposition or vasospasm. Twenty dogs were monitored for 1 hour after heparin administration and then assigned to a control (n = 7) or nicergoline-treated (n = 13; 1 mg/kg intravenously) group. In control dogs, cyclic reductions in flow continued unchanged for another hour, whereas in the treated group they were markedly decreased in 1 dog and completely abolished in the other 12 dogs. Aspirin (30 mg/kg intravenously) suppressed flow reductions in all control dogs, confirming the primary role of platelet aggregation in the phenomenon. This study provides a modified model of platelet-mediated thrombosis in stenosed coronary arteries. Furthermore, the results indicate that nicergoline can effectively interfere with platelet function in vivo. The potent antithrombotic activity exhibited by nicergoline might enhance the therapeutic usefulness of this vasodilator.

Animals↗
PubMed1984

Blood flow to infarct and surviving myocardium: implications regarding the action of verapamil on the acutely ischemic dog heart.

After coronary occlusion, myocardium originally supplied by the occluded vessel ultimately separates into infarct and surviving muscle. To clarify this process, evolution of collateral blood flow to infarct and to surviving myocardium was retrospectively analyzed after permanent left anterior descending occlusion in 24 closed chest dogs. Microspheres were injected before occlusion and 5 and 20 minutes and 4 hours after occlusion. Ten minutes after occlusion, dogs received either verapamil, 0.4 mg/kg, followed by 0.6 mg/kg per hour for 6 hours (n = 10) or equivalent saline solution (n = 14). These dogs were sacrificed 3 days later, the distribution of the occluded artery was defined by dye perfusion and infarcted myocardium was determined by triphenyltetrazolium staining of heart slices. Surviving muscle within the distribution of the occluded artery was divided into medial regions adjacent to the infarct (medial adjacent) and remote from the infarct (medial remote) and lateral regions adjacent to infarct (lateral adjacent) and remote from the infarct (lateral remote). In both control and verapamil groups, collateral flows in all regions increased significantly by 140 to 400% over 4 hours. However, the relative magnitude of collateral flow to different regions showed a consistent order: infarct less than medial adjacent less than medial remote less than lateral remote. There were no significant differences in regionally matched flows or size of infarction between control and verapamil-treated groups. Collateral perfusion begins to show distinctive patterns of change in infarct and surviving muscle very soon after coronary occlusion. Collateral flow within subdivisions of the occluded coronary artery bed increases as distance from the infarct increases, with lateral segments having higher flows than medial segments. This relation persists during the first 4 hours after occlusion. In this study, verapamil neither increased collateral flow to the occluded bed nor altered minimal flow requirements for myocardial survival.

Animals↗
PubMed1983

Preparation of monomeric cytochrome C oxidase: its kinetics differ from those of the dimeric enzyme.

Bovine cytochrome c oxidase in 0.1% dodecylmaltoside, 50 mM KCl and 10 mM Tris-HCl, pH 7.4 is monodisperse with an apparent Mr 360,000 (dimer) as estimated by filtration on Ultrogel AcA 34. In the absence of added KCl the apparent Mr is 160,000 (monomer). The dimeric enzyme has a high and a low affinity site for cytochrome c; the monomeric, only the high affinity site. The results are consistent with the existence of one active site per monomer, having high affinity for cytochrome c. Since in a dimer the two sites are in close proximity, the binding of the first molecule of cytochrome c to the first site hinders the binding of the second molecule to the second site. The kinetic data fit with a model of homotropic negative cooperativity. The effect of salts on the cytochrome c oxidase kinetics is also present in isolated bovine heart mitochondria.

Animals↗
PubMed1983

The effects of nitroglycerin-methoxamine combination on infarct size in conscious dogs.

The effect of nitroglycerin combined with methoxamine in reducing infarct weight was studied in conscious dogs. Ten minutes after permanent left anterior descending (LAD) coronary artery occlusion, 10 dogs received nitroglycerin (450 micrograms bolus IV, then 300 micrograms/min for 4 hours) and methoxamine as needed to maintain blood pressure and heart rate. No dogs in heart failure. Ten control dogs received saline solution. Dogs were sacrificed 3 days later. The region at risk of infarction was delineated by simultaneously perfusing the aortic root with Evans blue and the distal LAD artery with saline solution under equal pressures. Slices of stained hearts were incubated with tetrazolium to identify infarct. Total weight of left ventricle (LV), risk region, and infarct was measured. Nitroglycerin-treated dogs showed no difference from control dogs in infarct weight (26.2 +/- 5.9 gm +/- SE vs 27.7 +/- 5.6 gm), percent risk region/LV (36.0 +/- 1.4% vs 37.9 +/- 3.1%), or present infarct/LV (23.5 +/- 5.2% vs 24.8 +/- 4.9%). In a subgroup with risk region/LV less than or equal to 35%, nitroglycerin reduced infarct weight by 45% (8.8 +/- 8.5% vs 15.9 +/- 7.9%), percent infarct/LV by 49% (7.1 +/- 6.8% vs 13.8 +/- 6.6%), and percent infarct/risk region by 41% (23.0 +/- 22.0% vs 38.9 +/- 15.9%). Because of the small number of dogs in the study, differences were not significant. In dogs with risk region/LV greater than 35%, nitroglycerin had no effect. Thus, in dogs without overt heart failure, nitroglycerin may salvage ischemic tissue within small areas at risk of infarction, but the results are not definitive. However, our results clearly demonstrate that in the absence of failure, nitroglycerin does not reduce the size of large infarcts.

Animals↗
PubMed1983

Beneficial effects of the alpha-adrenergic antagonist nicergoline during acute myocardial ischemia and reperfusion in the dog.

Recent experimental and clinical data have stimulated interest in the use of alpha-adrenergic antagonists in acute myocardial infarction. We evaluated nicergoline, a new relatively selective alpha 1-antagonist which uniquely lowers heart rate. Open-chest dogs, randomized to control (n = 25) or intravenously treated group (n = 20; 0.5 mg/kg bolus, then 0.10 to 0.15 mg/kg/min), underwent coronary artery occlusion (CAO) followed after 25 minutes by coronary artery reperfusion (CAR). Nicergoline decreased heart rate by 47 +/- 5 bpm and mean aortic pressure by 39 +/- 4 mm Hg. Following CAO, nicergoline reduced total coronary collateral resistance (radiolabeled microspheres; 698 +/- 75 vs 2167 +/- 530 mm Hg/ml/min/gm, p less than 0.05), increased the ischemic zone/nonischemic zone flow ratio (0.14 +/- 0.04 vs 0.06 +/- 0.02, p less than 0.05), and reduced the rise in intramyocardial CO2 tension in the ischemic zone (mass spectrometry, p less than 0.001). Furthermore, the drug decreased the rate of ventricular tachycardia (VT; 191 +/- 13 vs 243 +/- 3 bpm, p less than 0.001) and the incidence of ventricular fibrillation (VF; 1 of 20 [5%] vs 7 of 25 [28%], p less than 0.05). Following CAR, nicergoline did not significantly reduce the incidence of VF but did lower rate (154 +/- 8 vs 212 +/- 10 bpm, p less than 0.001) and incidence (p less than 0.05) of VT. Thus nicergoline reduced severity of ischemia and afforded protection against arrhythmias induced by myocardial ischemia and reperfusion. The observed reduction in heart rate may have contributed importantly to these beneficial effects. Clinical investigation of this potentially useful vasodilator seems warranted.

Animals↗
PubMed1983

Early degradation of collagen after acute myocardial infarction in the rat.

After acute myocardial infarction (MI), proteolysis of necrotic myocardium is mediated by infiltrating inflammatory cells at the infarct margins. Collagen forms a structural fibroskeleton in healthy myocardium, and after MI this collagen may continue to provide significant tensile strength to the necrotic muscle wall. To determine whether collagen is also degraded (which might decrease infarct wall strength) and, if so, whether inflammatory cell proteases are implicated, hydroxyproline was measured from infarct zone and normal zone tissue from 24-hour infarcts produced in control rats and in rats made leukopenic (white blood cell count less than 300/mm3) by prior whole-body irradiation. Hydroxyproline was measured after precipitation of tissue homogenates with trichloroacetic acid to separate partially degraded collagen from larger collagen molecules that might retain structural importance. At 24 hours, there was significant (25%) collagen degradation in the infarct zone (p less than 0.01) in control rats but not in leukopenic rats. Tissue cell counts revealed a paucity of inflammatory cells in the infarct margins in leukopenic rats. Electron microscopic studies revealed greater preservation of collagen in the 24-hour-old infarcts of irradiated leukopenic rats compared with those of control rats. These results suggest that at 24 hours after experimental MI in the rat, there is significant collagen degradation mediated by inflammatory cell proteases.

Animals↗
PubMed1983

Role of cellular proteinases in acute myocardial infarction. I. Proteolysis in nonischemic and ischemic rat myocardium and the effects of antipain, leupeptin, pepstatin and chymostatin administered in vivo.

To test the hypothesis that cellular proteinases contribute to ischemic myocellular death, measurements were made of tyrosine release (an index of overall proteolysis) from incubated slices of nonischemic and ischemic myocardium obtained at various times after coronary artery occlusion in rats. Proteolysis failed to increase in ischemic myocardium throughout the first 24 hours of occlusion, when irreversible damage develops, indicating that cellular proteinases do not undergo generalized activation in this phase. These data represent the first assessment of myocardial proteolysis throughout the development of ischemic death, and suggest that cellular proteinases do not play a causal role in this process. However, the possibility remains that ischemia selectively accelerates the breakdown of vital proteins, a phenomenon that may not be detected by measuring overall proteolysis. To determine whether future studies on the effects of proteolytic inhibition on infarct size are feasible, the ability of the proteinase inhibitors antipain, leupeptin, pepstatin and chymostatin, given in vivo, to interfere with proteolysis in ischemic myocardium was also evaluated. Leupeptin (10 or 40 mg/kg) inhibited proteolysis in a dose-related fashion (-49 and -72%, respectively, p less than 0.001). Antipain (20 mg/kg) decreased protein breakdown by 60% (p less than 0.001). The combination of antipain (20 mg/kg), leupeptin (40 mg/kg) and pepstatin (5 mg/kg) suppressed proteolysis almost completely at both 15 minutes (-88%, p less than 0.001) and at 6 hours (-72%, p less than 0.05) of ischemia, that is, throughout the development of irreversible injury. These results demonstrate that whatever proteolysis is occurring during acute myocardial infarction is largely mediated by cathepsins A, B, D, L and H and by calcium-activated neutral protease (that is, the enzymes sensitive to the inhibitors used). Because antipain, leupeptin and pepstatin significantly suppress such proteolysis, these agents might be useful in further assessing any potential contribution of cellular proteinases to the production of ischemic myocellular death. In addition, this study provides a new experimental model that affords serial assessments of regional myocardial proteolysis during the evolution of myocardial infarction.

Animals↗
PubMed1983

Concealed antidromic re-entrance during rapid atrial pacing in the Wolff-Parkinson-White syndrome.

In a patient with Wolff-Parkinson-White syndrome, rapid atrial pacing up to rates of 140/min resulted in A-H prolongation; increases in rate up to 200/min, however, failed to lengthen A-H further. The delta-H interval increased as rate rose to 120/min, but remained stable thereafter. These and other findings suggest retrograde activation of the His bundle via the accessory pathway at rates greater than 140/min. Such a phenomenon: 1) prevents initiation of PSVT with atrial pacing; 2) prevents one from determining the anterograde block rate of the AV node; 3) represents concealed antidromic re-entrance, which may theoretically lead to antidromic re-entrant PSVT.

Atrial Fibrillation↗
PubMed1981

Isolation and characterization of polysomes from thylakoid membranes of Chlamydomonas reinhardii.

Chloroplast polysomes that were originally bound to thylakoid membranes were isolated from the cell wall mutant CW-15 from Chlamydomonas reinhardii. Polysomes were isolated from synchronously grown cells harvested in the middle of the third light period, when the ratio of chloroplast to cytoplasmic polysomes was maximal. Thylakoid membranes were isolated from a chloroplast fraction and polysomes were released by Triton X-100. Analyses of subunits on sucrose gradients showed that the polysomes consisted predominantly of the 70 S-type ribosomes. The detached polysomes as well as polysomes still bound to the thylakoid membrane were active in in vitro protein synthesis when supplemented with Escherichia coli-soluble factors. The in vitro activity was inhibited by chloramphenicol and aurintricarboxylic acid, but not by cycloheximide.

Cell Fractionation↗