1992 ISHR American Section Scientific sessions highlights [cardiac myocytes: coronary circulation: myocardial ischemic injury and protection: heart failure].
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Animals↗
Biomedical subjects
R W Millard
Publications and source records attributed to R W Millard.
Demonstration of hydroxyl radical and its role in hydrogen peroxide-induced myocardial injury: hydroxyl radical dependent and independent mechanisms.
We investigated the mechanism of hydrogen peroxide (H2O2) action on myocardial injury in relation to hydroxyl radical (.OH) formation. Isolated rat hearts were perfused with a concentration of H2O2 (300 microM) known to produce cardiac injury. Perfusion of H2O2 for 15 min caused severe myocardial dysfunction, morphological damage, ATP depletion, and lipid peroxidation. Hydrogen peroxide concentration in the coronary effluent was reduced approximately 40% reflecting a myocardial H2O2 consumption of 12.7 +/- 0.9 mumol/15 min/g wet tissue (n = 12). One of the .OH-generated derivatives, 2,3-dihydroxybenzoic acid (2,3-DHBA), formed from reaction with salicylic acid, was detected in the coronary effluent by high-performance liquid chromatography at 23.16 +/- 4.05 nmol/15 min/g wet tissue. Catalase (200 U/ml, n = 6) added to the perfusate attenuated all parameters of myocardial injury by eliminating H2O2 from the perfusate, and thus .OH was not detected in the effluent. Deferoxamine (5 mM, n = 7) added to the perfusate reduced morphological damage and lipid peroxidation, but not dysfunction or ATP depletion. Deferoxamine significantly reduced .OH production; 2,3-DHBA was 5.22 +/- 3.56 nmol/15 min/g wet tissue. The present study provides evidence that .OH is produced in the H2O2-perfused heart. The adverse H2O2-mediated myocardial outcomes documented in this study appear to arise from both .OH-dependent and .OH-independent mechanisms.
Adenosine Triphosphate↗
Cardiovascular system design and barosaurus.
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Animals↗
Compliance to nicotine gum recommendations in a multicomponent group smoking cessation program: an exploratory study.
This is an exploratory study of compliance to nicotine chewing gum in a multicomponent group smoking cessation program where usage was optional. Two-thirds (24 out of 36) of the participants across three group sessions complied with the recommendation to use nicotine chewing gum. All subjects received standard instructions. Demographic characteristics (age, sex, site of employment) and smoking variables (number of years smoked, pretreatment number of cigarettes smoked per day, and nicotine dependence) failed to predict compliance, but complaint participants reported significantly greater confidence at their ability to not smoke in various challenging situations as measured by the Smoking Self Efficacy Questionnaire. Those who did comply mostly failed to chew the gum in the way instructed. Reduced craving was cited as the most positive feature of gum use.
Adult↗
Quantitation of perfluorocarbon blood substitutes in tissues using F-19 magnetic resonance spectroscopy.
F-19 Magnetic Resonance Spectroscopy (MRS) has been used to quantitate the biodistribution of perfluorocarbon (PFC) blood substitutes in porcine tissues following intraperitoneal administration of a 20% w/v perfluorotributylamine (FC-43) based emulsion. PFC tissue concentrations were determined for spleen, liver and lung tissues from juvenile pigs ranging in weight from 12 to 15 kg. Typical average values (mmoles FC-43/gram tissue) ranged from 0.23-0.39 for spleen; 0.09-0.13 for liver; and 0.09-0.12 for lung. A description of this spectroscopy based quantitation technique will be presented. F-19 MRS is a specific, rapid, and accurate method for measurement of PFC tissue concentrations.
Animals↗
A comparison of models describing reports of disability associated with chronic pain.
We examined pain-related disability from two perspectives. A disability model, suggesting that disability is a direct consequence of pain, is compared with a symptom perception model emphasizing individual differences in perception and report of physical symptoms. Disability estimates (reported activity interference and employment status) were obtained from a sample of 179 patients with chronic pain. Using multiple regression analyses, we showed that distress, symptom reporting, and pain intensity accounted for comparable levels of variance in reports of activity interference. When we controlled for distress, the frequency of reporting physical symptoms made the largest contribution to prediction of this kind of disability (14%). Neither symptom report or pain intensity was useful in predicting the more objective disability criterion of employment status. Results were interpreted as probable evidence against a disability model of pain-related disability and suggest the relative importance of individual cognitive differences in symptom responsivity.
Activities of Daily Living↗
Construct validity of practical questionnaires for assessing disability of low-back pain.
Four practical questionnaires used for assessing disability associated with chronic low-back pain were investigated. Comparison of findings among 93 patients disclosed a moderate level of agreement (r = 0.44-0.63) between the scales, providing limited evidence that a single construct is being measured by each. The questionnaires were more strongly related to each other than to psychosocial scales, which suggests that findings are distinguishable from distress. However, higher distress was significantly associated with greater reports of disability. This was most discernible in the form of more enduring characteristics that may reflect neuroticism. These findings allow modest support for the construct validity of the four questionnaires and suggest a need for caution with their use because persistently negative affect may be a biasing factor.
Adult↗
Hemodynamic and electrophysiologic effects of amlodipine, a new calcium channel blocker.
The effects of amlodipine (300 micrograms/kg administered intravenously), a new, long-acting, dihydropyridine class, calcium channel blocking drug, were studied in atrially paced (120 beats/min), autonomically blocked dogs. Hemodynamic and electrophysiologic parameters were measured before and up to 3 hours after amlodipine. Coronary blood flow was significantly increased 10 and 30 minutes after drug administration, whereas cardiac output and mean arterial pressure were unaffected. Coronary vascular resistance was decreased but total systemic vascular resistance did not change. Atrioventricular (AV) nodal conduction was slightly prolonged, as reflected by increases in atrial-His bundle and AV conduction times and PR interval, 30 minutes after administration. All parameters returned toward their control values within 3 hours after drug administration. Comparison of coronary vascular resistance and AV conduction changes with those previously reported for other calcium channel blocking drugs where autonomic blockade existed suggests that at equivalent levels of coronary vasodilation, amlodipine's effects more closely resemble the effects of diltiazem or verapamil than other dihydropyridines.
Amlodipine↗
Amlodipine, a long-acting calcium antagonist drug reduces ischemia-induced ventricular conduction delay in pig hearts.
The effects of amlodipine, a novel, long-lasting calcium channel blocking agent, on ischemia-induced myocardial conduction delay was studied in anesthetized pigs paced at a constant heart rate. Acute coronary occlusion (3 minutes) significantly lengthened time to onset, time to peak and duration of bipolar electrograms recorded from both subendocardial and subepicardial left ventricular sites. After intravenous injection of amlodipine (0.3 mg/kg, n = 6), subsequent periods of ischemia greatly reduced (p less than 0.01) all indexes of subepicardial conduction delay. In the subendocardium, amlodipine decreased only time to onset (-25 +/- 4%, p less than 0.01) within the ischemic zone. Significant delays in all indexes were present during repeated ischemic periods in the placebo-treated control group (n = 5). Amlodipine also increased regional myocardial blood flow within the nonischemic myocardium by 25 +/- 10% and decreased mean aortic pressure by 7 +/- 2% without altering flow in the ischemic region. Left atrial pressure remained unchanged. Indexes of ischemia-induced conduction delay were more rapidly restored after reperfusion in amlodipine-pretreated than in control animals. In conclusion, amlodipine produced a beneficial blood flow-independent effect on ischemia-induced injury potentials. The effect may help to reduce the likelihood of development of lethal ventricular arrhythmias in the early stage of myocardial ischemia in the clinical setting.
Amlodipine↗
Protection of regional mechanics and mitochondrial oxidative phosphorylation by amlodipine in transiently ischemic myocardium.
The effects of amlodipine (0.3 mg/kg administered intravenously, n = 5) and placebo (n = 5) on recovery of myocardial function and respiration of isolated mitochondria were examined in "stunned" myocardium of normotensive pentobarbital-anesthetized dogs. Measures of myocardial wall motion, using sonomicrometers, and tissue blood flow, by radioactive microspheres, were obtained at baseline, 15 minutes after administration of amlodipine or placebo, after 10 minutes of left circumflex artery ligation and at 60 minutes of reperfusion. Mean aortic pressure decreased from 115 +/- 6 to 101 +/- 5 mm Hg after administration of amlodipine and remained decreased throughout the experiment. Heart rate was not significantly affected at any time. Both groups showed similar degrees of ischemia: elevation of ST segment to 4.7 +/- 1.4 vs 6.2 +/- 1.9 mV; reduction of ischemic zone shortening fraction to 0.6 +/- 1.9 vs -3.4 +/- 2.7%; and reduction of epicardial and endocardial blood flows (epicardial = 40 +/- 13 vs 43 +/- 13 ml/100 g/min; endocardial = 7 +/- 4 vs 13 +/- 6 ml/100 g/min [values for amlodipine vs placebo]). Mitochondrial state 3 rate of respiration and respiratory control index indicative of rate of adenosine triphosphate synthesis and membrane integrity in myocardial samples taken after 10 minutes of ischemia were significantly reduced in the placebo but not in the amlodipine group. Myocardial function showed significantly greater improvement in amlodipine vs placebo at 60 minutes of reperfusion as indicated by shortening fraction (17.7 +/- -1.4 vs 5.8 +/- -3.5%, amlodipine vs placebo), which may have been related to increased myocardial blood flow and decreased blood pressure during reperfusion. Thus, amlodipine pretreatment prevented mitochondrial dysfunction during ischemia and accelerated recovery of both myocardial mechanical function and blood flow when compared with placebo.
Amlodipine↗
Effects of calcium channel antagonists on carotid sinus baroreflex control of arterial pressure and heart rate in anesthetized dogs.
Our study was designed to determine whether the calcium channel antagonists verapamil, diltiazem, and nifedipine and the nitrate vasodilator sodium nitroprusside modulate carotid sinus (CS) baroreflex control of mean arterial pressure (MAP) and heart rate (HR). Pentobarbital-anesthetized, vagotomized dogs were surgically prepared for reversible vascular isolation of the CS regions. Open-loop performance of the CS baroreflex was determined under control conditions and after intravenous infusion of each agent for 20 minutes at four rates (nitroprusside: 0.3-10 micrograms/kg/min; verapamil and diltiazem: 1-30 micrograms/kg/min; nifedipine: 0.1-3 micrograms/kg/min). With the CS baroreflex loop closed, each vasodilator decreased MAP from control (nitroprusside: 127 +/- 3 to 69 +/- 5 mm Hg; verapamil: 137 +/- 7 to 86 +/- 5 mm Hg; diltiazem: 137 +/- 9 to 100 +/- 5 mm Hg; nifedipine: 140 +/- 6 to 109 +/- 7 mm Hg). Each compound also caused a dose-dependent downward shift in the open-loop CSP-MAP relations. The higher doses of each vasodilator also depressed the total range of control of MAP (i.e., maximum MAP minus minimum MAP) by the baroreflex and significantly attenuated the peak open-loop MAP/CSP gains (nitroprusside: 1.21 +/- 0.19 to 0.56 +/- 0.12; verapamil: 1.36 +/- 0.16 to 0.64 +/- 0.10; diltiazem: 1.52 +/- 0.34 to 0.89 +/- 0.11; nifedipine: 1.35 +/- 0.20 to 0.83 +/- 0.14) but did not alter the CSP at which the peak gain was manifest. Only verapamil and diltiazem significantly shifted downward the CSP-HR relations, whereas none of the drugs affected the total range of baroreflex control of HR (i.e., maximum HR minus minimum HR) or the peak open-loop HR/CSP gains. Our results suggest that 1) it is unlikely that calcium channel antagonists act directly on the baroreceptors or the neural components of the baroreflex loop (i.e., afferent, central and efferent nerves) because they impair CS baroreflex control of MAP but not HR and 2) the impairment of MAP control is predominantly due to a nonspecific blunting of adrenergic vasoconstriction.
Animals↗
The Functional Assessment Screening Questionnaire: application for evaluating pain-related disability.
The Functional Assessment Screening Questionnaire (FASQ) is a 15-item checklist which was developed for primary care populations and may serve as a questionnaire method for evaluating disability which is associated with chronic pain. One hundred fifty-eight patients completed the FASQ as part of an initial multidisciplinary evaluation of chronic pain. Reliability was reaffirmed through split-half and alternate-form methods. Responses were examined to explore relationships to aspects of disability. Although job functions were not directly assessed, the scores of employed vs unemployed respondents differed significantly. Findings were related to Minnesota Multiphasic Personality Inventory scale scores but appeared to reflect a separate phenomenon. Scale 1 (Hs) was the most useful scale for predicting level of reported impairment. Nonparametric methods showed levels of functioning varying significantly by site of pain complaint. Patients with back pain reported the most difficulty; those with head pain and genital pain reported the least difficulty. An internal structure appropriate to chronic pain populations was discerned, with two general factors measuring either physical-motoric or cognitive-social aspects of disability. Aside from constraints associated with the use of self-report methods, the FASQ may be helpful as part of efforts to portray pain-related disability.
Activities of Daily Living↗
Microcirculatory effects of somatostatin in acute pancreatitis.
Somatostatin, a 28-amino-acid inhibitory polypeptide has been advocated for the treatment of upper gastrointestinal bleeding and acute pancreatitis. This study examines the effect of somatostatin in acute hemorrhagic pancreatitis in piglets (n = 12), weighing 8-12 kg. Six animals served as controls, and received only fluid resuscitation (0.9%, NaCl, 20 ml/kg/h). Six animals received somatostatin treatment consisting of a 15 micrograms/kg bolus i.v. given simultaneously with the induction of pancreatitis, and treatment continued with an intravenous infusion (15 micrograms/kg/h) for 5 h. Cardiac output, heart rate, blood pressure, arterial pO2, hematocrit and serum amylase were recorded before and each hour during the experiment. Regional blood flow in the gastrointestinal area was measured using the microsphere method. The microspheres labelled with three different isotopes were administered before the experiment and at 2 and 5 h, respectively. There was a significant decrease in the cardiac output (p less than 0.05) and an increase in systemic blood pressure in the somatostatin-treated group (p less than 0.025). Pancreatic blood flow decreased by 43% following somatostatin infusion. The decreases at 2 and 5 h were highly significant (p less than 0.005). Blood flow to the mucosal but not muscular region of the stomach was decreased by somatostatin. This study suggests that somatostatin might be harmful in acute pancreatitis due to its adverse effects on pancreatic blood flow and cardiac output. However, somatostatin may be effective in reducing gastrointestinal bleeding. If the drug is used clinically, careful monitoring of the cardiac output is necessary.
Acute Disease↗
Sympathetic innervation of the cardiovascular system in the giraffe.
The extreme blood pressure gradients in the giraffe, produced by gravity and behaviour, present a special challenge to blood flow and vascular capacity regulation, e.g. via sympathetic nerves. We report the distribution of nerves in vascular tissue from giraffe extremities and neck based on immunofluorescence against specific antisera to dopamine-beta-hydroxylase, neuropeptide Y, neurofilament, and synapsin I. Sympathetic innervation of gravitation-dependent arteries in the limbs was restricted to the adventitia-media border, while in carotid arteries fibers penetrated deep into the media. Surprisingly, limb veins appeared to be devoid of sympathetic innervation, while jugular veins had a sparse innervation. The morphological response, medial hypertrophy, that parallels the hydrostatic pressure gradients in the circulation combines with the thick skin and tight underlying fascia, the 'g-suit', and an exquisitely distributed sympathetic innervation pattern to provide an effective array of mechanisms for cardiovascular regulation in the adult giraffe.
Animals↗
Studies on the mode of action of isosorbide dinitrate: a physiologic and biochemical approach.
The action of isosorbide dinitrate (ISDN) and diltiazem on coronary artery diameter, vascular resistance, and coronary blood flow was determined in instrumented postoperative conscious dogs. Low doses of ISDN were found to increase the diameter of large arteries without affecting coronary blood flow. Higher doses of ISDN produced an increase in both coronary diameter and blood flow. Diltiazem, on the other hand, increased coronary artery diameter and blood flow at all doses tested. Coronary vascular resistance was more sensitive to diltiazem than to ISDN. In isolated canine cardiac Purkinje strands, ISDN produced a concentration-dependent decrease in force development and action-potential duration measured at 50% of repolarization (APD50). ISDN did not significantly affect action potentials recorded in Purkinje strands depolarized by potassium (22 mmol) and treated with isoproterenol (10(-6)M). Diltiazem also decreased Purkinje strand force development and APD50 in a concentration-dependent manner. Diltiazem, however, was several orders of magnitude more potent than ISDN and completely abolished action-potential genesis in potassium-depolarized, isoproterenol-restored Purkinje strands. Both diltiazem and ISDN were found to relax porcine coronary artery strips contracted by KCl or histamine. Studies on 45Ca flux, in isolated coronary artery rings, indicate that ISDN inhibited both histamine-induced Ca++ influx and efflux from intracellular sources. The inhibition of Ca++ efflux and intracellular Ca++-dependent contraction occurred over a similar ISDN concentration range. ISDN also relaxed bovine coronary artery strips contracted with KCl. No change in cyclic adenosine monophosphate levels occurred during ISDN-induced relaxation of bovine coronary arterial strips.(ABSTRACT TRUNCATED AT 250 WORDS)
Action Potentials↗
Prevention of lactate production and myocyte injury in isolated rat hearts perfused with perfluorochemical emulsion.
The ability of an oxygenated perfluorocarbon (PFC) emulsion to prevent early signs of myocardial cell stress associated with Krebs-Henseleit (KH) perfusion was evaluated in isolated rat hearts supported in a Langendorff apparatus. Throughout the two-hour perfusion, hearts in both perfusion groups had similar left ventricular pressure and rates of left ventricular pressure development (dP/dt). After 2 h, coronary perfusate flow was 6.6 +/- 1.0 ml/min in the KH group and 2.2 +/- 0.1 ml/min in the PFC group. Oxygen content was 1.5 +/- 0.1 ml/100 ml and 3.4 +/- 0.1 ml/100 ml, in KH and PFC groups, respectively. Perfusate lactate levels rose from zero to 24.0 +/- 8.0 microgram/ml in the KH group and to 10.0 +/- 3.0 micrograms/ml in the PFC group. Reduction in myocardial cell injury and in total calcium content was also observed in hearts perfused with PFC emulsion. At the electron microscopic level, mitochondrial structure was preserved in both normal and injured myocytes of hearts perfused with PFC. We conclude that early signs of anaerobic metabolism are retarded by perfusion with PFC emulsions and that ventricular contractile performance is maintained at approximately one-half coronary perfusate flow in the PFC hearts. The mechanism whereby coronary flow is regulated downward in the PFC perfused hearts remains unanswered.
Animals↗
Defining the mechanical border zone: a study in the pig heart.
Wall motion abnormalities can occur in nonischemic areas contiguous with ischemic myocardium. The extent of the mechanical border zone contiguous with an acute myocardial ischemic region was mapped in eight open-chest anesthetized pigs using sonomicrometer crystals implanted parallel with the visible ischemic border in the subepicardium of ischemic (IZ), proximal border (BZ1), distal border (BZ2), and remote normal (NZ) zones. Regional systolic shortening fraction was near 15%, and epicardial blood flow was approximately 1.5 ml X min-1 X g-1 in all locations before ischemia was induced. Blood flow fell to less than 0.05 ml X min-1 X g-1 and the left ventricular free wall supplied by the distal one-third of the left anterior descending artery exhibited holosystolic lengthening when the vessel was occluded. After occlusion, systolic shortening fraction was depressed by 45% in the BZ1 located 3.1 +/- 1.1 mm from the ischemic margin and by 25% in the BZ2, which was measured at 9.3 +/- 1.5 mm from the ischemic margin without significant flow reduction. The NZ, 22.3 +/- 4.6 mm from ischemic margin, was unaffected by occlusion. Computer analysis of the data shows that wall motion is depressed as far as 12 mm from the ischemic margin. This abnormal wall motion surrounding focal transmural myocardial ischemia is presumed to result from mechanical tethering.
Animals↗
Coronary blood flow and myocardial segment dimensions during simulated dives in seals.
Three harbor seals Phoca vitulina richardsi and five spotted seals Phoca vitulina largha were used in studies of acute episodes of local myocardial ischemia in open-chest, anesthetized animals and of coronary blood flow and regional function as indicated by left ventricular segment dimensions during experimentally simulated dives of conscious, instrumented animals. We observed that seal myocardium, in which there are few coronary anastomoses, responded to brief local occlusion with prompt local dysfunction and systolic bulging; coronary flow in the nondiving seal oscillated irregularly and declined with spontaneous apnea and related falling heart rate; flow continued to oscillate but was much reduced during dives, frequently ceasing entirely for periods as long as 45 s; ventricular segment dimension shortening was reduced intermittently during dives; and elevated heart rate induced during dives by cardiac pacing or by administration of atropine diminished or eliminated the reductions in coronary blood flow. Responses of seal heart reflect the reduction in cardiac metabolic demand during diving and the seal's myocardial adaptation for enhanced anaerobic glycolysis. The seal heart can maintain mechanical function during dives with minimal coronary perfusion, despite the progressive and ultimately profound hypoxia, hypercapnia, and acidosis. Reduced cardiac metabolism, copious glycolytic reserves, and metabolite washout by intermittent brief bursts of coronary blood flow are apparently sufficient to support continued cardiac function, even though the seal heart has little tolerance for acute localized ischemia.
Animals↗