Biomedical subjects

M O Jeroudi

Publications and source records attributed to M O Jeroudi.

13 recordsLinked to original sources

PubMed1990

Percutaneous transluminal coronary angioplasty in octogenarians.

OBJECTIVE: To assess the safety and short- and long-term outcomes of percutaneous transluminal coronary angioplasty in octogenarians. DESIGN: Retrospective chart review of clinical series. SETTING: Referral-based university medical center. PATIENTS: Consecutive series of 54 octogenarian patients (mean age, 82.4 years) who had percutaneous transluminal coronary angioplasty between March 1980 and December 1988. Of these patients, 91% presented with severe angina (Canadian Cardiovascular Society Class III or IV); 59% had unstable angina. Twenty-six patients (48%) had had a previous myocardial infarction and 15 (28%) had had previous coronary artery bypass surgery. Multivessel disease was present in 44 patients (81%). Follow-up ranged from 1 to 50 months (mean, 19 months). INTERVENTION: Percutaneous transluminal coronary angioplasty. MEASUREMENTS AND MAIN RESULTS: The angiographic success rate was 50 of 54 (93%; 95% CI, 81% to 98%) and the clinical success rate was 49 of 54 (91%; CI, 79% to 97%). Two patients had procedure-related myocardial infarction. Two patients died in the hospital, 1 from cardiac tamponade because of pacemaker perforation and 1 from cardiogenic shock after a myocardial infarction despite successful angioplasty. During the follow-up period 4 patients required bypass surgery, 2 had myocardial infarction, and 7 died (4 deaths were cardiac). Eleven patients (20%) had re-stenosis, 7 of whom were managed with repeat angioplasty, including 1 patient who had four procedures. At follow-up, 42 of 45 survivors (93%) were asymptomatic or had class II angina. The Kaplan-Meier survival for all patients, including those who died in the hospital, was 87% at 1 year and 80% at 3 years. Cumulative freedom from major cardiac events (death, myocardial infarction, or coronary bypass surgery) was 81% at 1 year and 78% at 3 years. CONCLUSIONS: Percutaneous transluminal coronary angioplasty can be done in octogenarians with a high rate of angiographic and clinical success, low complication rate, and a favorable long-term (3-year) outcome. As such, it is a treatment option in managing advanced coronary artery disease in this fragile group of patients.

Age Factors↗

PubMed1990

An accurate, nontraumatic ultrasonic method to monitor myocardial wall thickening in patients undergoing cardiac surgery.

Measurement of systolic wall thickening by sonomicrometry provides an accurate index of regional left ventricular function, but the trauma of crystal insertion limits its widespread clinical use. The first clinical application of a 10 MHz ultrasonic Doppler probe that can be either sutured or applied by suction to the epicardium and can measure wall thickening at any depth of the left ventricular wall is described. In 18 dogs, measurements obtained with the suction probe correlated well (r = 0.97) with those of a previously validated sutured probe. To assess clinical feasibility, the probe was applied to the epicardium of patients undergoing coronary bypass surgery. Good quality wall thickening signals were obtained with no complications. Transmural left ventricular thickening fraction before bypass surgery was 34 +/- 3% (mean value +/- SE) at the mid-ventricular lateral wall, 33 +/- 4% at the anterior basal wall and 26 +/- 4% at the mid-ventricular posterior wall. Right ventricular thickening fraction averaged 25 +/- 3%. Endocardial thickening fraction tended to exceed epicardial thickening fraction, although the difference attained statistical significance (p less than 0.05) only at the anterior basal wall. On average, thickening fraction during the immediate postoperative period remained unchanged compared with the preoperative values, but a marked individual variability was observed, with 7 of 15 patients exhibiting a decrease and 8 an increase. Exteriorization of the wires attached to the sutured probe allowed continuous in situ monitoring of wall thickening in the postoperative period and subsequent removal of the probe. In six patients the crystal was left in place for 48 to 72 h after surgery and then removed without complications; good wall thickening signals were obtained for the entire period during which the probe was implanted. Thus, the Doppler probe is an accurate, atraumatic method for measuring right and left ventricular regional function. Transmural, endocardial and epicardial function can be mapped at various sites during surgery, and post-operatively one can monitor serial changes of regional function and assess the effects of cardioplegia and other therapeutic interventions. This technique should be useful for both investigative and clinical purposes.

Adult↗

PubMed1990

Effect of human recombinant superoxide dismutase on canine myocardial infarction.

To determine whether human recombinant superoxide dismutase (h-SOD) produces sustained reduction of infarct size, anesthetized dogs underwent a 2-h coronary occlusion followed by either 48 or 4 h of reperfusion. In the 48-h study, dogs were randomized to three intravenous treatments: 1) "low-dose" h-SOD (2 mg/kg bolus 2 min before reperfusion followed by 4 mg/kg over 45 min), 2) "high-dose" h-SOD (8 mg/kg bolus 2 min before reperfusion followed by 8 mg/kg over 45 min), or 3) equivalent volumes of saline. In the 4-h study, dogs were randomized to high-dose h-SOD or saline. Occluded bed size was measured by postmortem perfusion and infarct size by triphenyl tetrazolium chloride staining and planimetry. Investigators performing the study and measuring infarct size were blinded to the treatment given. High plasma concentrations of h-SOD were present in the arterial blood of treated dogs in the early phase of reperfusion (greater than 60 and greater than 180 micrograms/ml in low- and high-dose groups, respectively). In both studies, control and treated groups were similar with respect to occluded bed size, collateral blood flow, and rate-pressure product during ischemia. In the 48-h study, infarct size, expressed as percent of occluded bed size, was 41.3 +/- 7.6% (mean +/- SE) in the control group, 37.1 +/- 7.2% in the low-dose h-SOD group, and 48.0 +/- 7.1% in the high-dose h-SOD group. In the 4-h study, infarct size was 30.6 +/- 4.9% in the control group and 31.5 +/- 9.6% in the high-dose h-SOD group. Analysis of the flow-infarct relationships confirmed that h-SOD did not reduce infarct size at any level of collateral flow in either the 48- or 4-h study. Recovery of regional myocardial function after reperfusion was also unaffected by h-SOD in both studies. Thus in this randomized blinded study, large doses of h-SOD given at the time of reperfusion failed to limit infarct size or enhance recovery of function, both early (4 h) and late (48 h) after reperfusion following a 2-h coronary occlusion.

Animals↗

PubMed1990

Effect of superoxide dismutase and catalase, given separately, on myocardial "stunning".

Controversy persists regarding which oxygen metabolites are cytotoxic. Although the combination of superoxide dismutase (SOD) and catalase has been shown to attenuate postischemic myocardial dysfunction ("stunning"), it is unknown whether this beneficial effect is due to scavenging of O2-., H2O2, or both. Accordingly, 85 open-chest dogs underwent a 15-min occlusion of the left anterior descending coronary artery followed by 4 h of reperfusion. In phase A, dogs received an intravenous infusion of saline (group I), SOD (5 mg/kg, group II), catalase (12,000 U/kg, group III), or the combination of SOD and catalase (same doses, group IV). Recovery of regional myocardial function (assessed as systolic wall thickening) after reperfusion was significantly improved by the combination of SOD and catalase but not by SOD alone or catalase alone. To determine whether higher doses of enzymes are more effective, in phase B dogs received an intracoronary infusion of normal saline (group V), SOD in low dose (1.5 mg/kg, group VI), SOD in high dose (6.3 mg/kg plus 1.5 mg/kg iv, group VII), catalase in low dose (18,000 U/kg, group VIII), or catalase in high dose (240,000 U/kg plus 40,000 U/kg iv, group IX). Despite the fact that the local plasma levels of enzymes were considerably higher than those achieved in phase A, none of the treatments in phase B significantly enhanced recovery of contractile function. This study demonstrates that the combination of SOD and catalase is more effective than either enzyme alone in attenuating postischemic myocardial dysfunction and that increasing the doses of SOD or catalase does not provide additional protection. The results suggest that both O2-. and H2O2 contribute significantly to the pathogenesis of myocardial stunning after regional ischemia in the intact animal. Furthermore, the data imply that if SOD and catalase are to be used clinically to prevent postischemic dysfunction, protection may be achieved most effectively by combining the two enzymes.

Animals↗

PubMed1990

Iron-mediated radical reactions upon reperfusion contribute to myocardial "stunning".

Recent evidence suggests that postischemic myocardial dysfunction ("stunning") is mediated by iron-catalyzed free radical reactions, but the exact time window during which the critical iron-mediated damage develops remains unknown. Furthermore, the evidence that iron promotes free radical reactions in vivo is indirect. Thus open-chest dogs undergoing a 15-min coronary occlusion and 4 h of reperfusion were given one of the following intracoronary infusions: desferrioxamine (DF) beginning 2 min before reperfusion (group I), DF beginning 1 min after reperfusion (group II), iron-loaded DF in dosage identical to group I (group III), or vehicle (controls, group IV). Recovery of contractile function was substantially greater in group I than in controls, whereas in groups II and III it was indistinguishable from controls. To determine whether the protection afforded by DF was due to inhibition of free radical reactions, myocardial production of free radicals was directly assessed by intracoronary infusion of the spin trap alpha-phenyl N-tert-butyl nitrone (PBN). In controls (group VI), radical adducts of PBN were released in the coronary venous blood after reperfusion. DF given as in group I (group V) markedly suppressed myocardial production of PBN adducts. These results strongly suggest that a substantial portion of the damage responsible for myocardial stunning is caused by iron-catalyzed free radical reactions that develop in the initial seconds of reperfusion and can be prevented by administration of iron chelators started just before reflow. Furthermore, the results demonstrate that attenuation of postischemic dysfunction by DF is associated with attenuation of free radical reactions in vivo, thereby providing direct evidence for a pathogenetic role of iron-catalyzed free radical reactions in myocardial stunning in the intact animal.

Animals↗

PubMed1990

Prolonged impairment of coronary vasodilation after reversible ischemia. Evidence for microvascular "stunning".

Reperfusion after brief, reversible myocardial ischemia is associated with prolonged depression of contractile function (myocardial "stunning"); however, the effect on coronary vascular function has not been defined. Thus, open-chest dogs (n = 14) underwent a 15-minute left anterior descending coronary artery (LAD) occlusion followed by reflow. Four hours after reperfusion, regional myocardial blood flow (microspheres) was significantly (p less than 0.01) lower and coronary vascular resistance significantly (p less than 0.01) higher in the postischemic as compared with the nonischemic endocardium. Furthermore, during maximal vasodilation elicited by intravenous adenosine (n = 6), myocardial blood flow was lower (p less than 0.05) and coronary vascular resistance higher (p less than 0.05) in the postischemic as compared with the nonischemic myocardium, both in the endocardial and in the epicardial layers. Similarly, during maximal dilation elicited by intravenous papaverine (n = 8), myocardial blood flow was lower (p less than 0.05) and vascular resistance higher (p less than 0.05) in the postischemic as compared with the nonischemic endocardium; a directionally similar trend was observed in the epicardium. Four hours after reperfusion, all indexes of reactive hyperemia after a 40-second coronary occlusion were significantly lower in the LAD than in the control circumflex coronary artery (n = 8). There was no appreciable correlation between systolic wall thickening in the stunned myocardium and 1) the resting myocardial perfusion, 2) the hyperemia attained during adenosine or papaverine, and 3) the hyperemic response to a 40-second coronary occlusion. In control dogs that did not undergo a 15-minute LAD occlusion (n = 15), there were no differences in myocardial blood flow or vascular resistance between the LAD-dependent and the circumflex-dependent bed, either before or during adenosine (n = 7) or papaverine (n = 8). Furthermore, reactive hyperemia after a 40-second occlusion did not differ between the LAD and the circumflex artery (n = 8). In conclusion, a brief (15 minute), reversible ischemic insult causes a prolonged increase in resting vascular resistance and a prolonged impairment in vasodilator responsiveness, both of which persist for at least 4 hours. The severity of these vascular derangements is not related to the severity of contractile depression, suggesting that they may represent a relatively independent phenomenon. It is proposed that, in addition to myocardial "stunning," reversible ischemia also causes a microvascular "stunning."

Adenosine↗

PubMed1989

Direct evidence that oxygen-derived free radicals contribute to postischemic myocardial dysfunction in the intact dog.

Electron paramagnetic resonance (EPR) spectroscopy was used to investigate whether (i) the free radicals produced in the "stunned" myocardium (myocardium with postischemic contractile dysfunction) are derived from O2, (ii) inhibition of radical reactions improves function, and (iii) i.v. spin traps are effective. Open-chest dogs undergoing a 15-min coronary occlusion received an i.v. infusion of the spin trap, alpha-phenyl N-tert-butylnitrone (PBN) (50 mg/kg). In group I (n = 6), EPR signals characteristic of radical adducts of PBN appeared in the coronary venous blood during ischemia and increased dramatically after reperfusion. In group II (n = 6), which received PBN and i.v. superoxide dismutase (SOD; 16,000 units/kg) plus catalase (12,000 units/kg), myocardial production of PBN adducts was undetectable during ischemia (delta = -100%, P less than 0.01 vs. group I) and markedly inhibited after reperfusion (delta = -86%, P less than 0.001). This effect was seen at all levels of ischemic zone flow but was relatively greater in the low-flow range. In group III (n = 8), the same dosages of SOD and catalase without PBN markedly enhanced contractile recovery (measured as systolic wall thickening) after reperfusion [P less than 0.01 at 3 hr vs. controls (group IV, n = 7)]. Systemic plasma activity of SOD and catalase averaged 127 +/- 24 and 123 +/- 82 units/ml, respectively, 2 min after reperfusion. PBN produced no apparent adverse effects and actually improved postischemic contractile recovery in group I (P less than 0.05 at 3 hr vs. controls). This study shows that (i) SOD and catalase are highly effective in blocking free radical reactions in vivo, (ii) the radicals generated in the "stunned" myocardium are derived from univalent reduction of O2, and (iii) inhibition of radical reactions improves functional recovery. The results provide direct, in vivo evidence to support the hypothesis that reactive oxygen metabolites play a causal role in the myocardial "stunning" seen after brief ischemia.

Animals↗

PubMed1989

Nonuniform transmural recovery of contractile function in stunned myocardium.

With the use of an epicardial Doppler probe, systolic wall thickening was selectively measured in the inner, mid, and outer layers of the left ventricular (LV) wall in 16 conscious dogs undergoing a 15-min left anterior descending artery (LAD) occlusion followed by 7 days of reperfusion (REP). Under control conditions, percent thickening fraction (ThF) was significantly greater (P less than 0.01) in the inner layer [36.0 +/- 2.3% (mean +/- SE)] than in the mid (28.6 +/- 2.1%) or outer (21.3 +/- 2.2%) layers. During LAD occlusion, 11 dogs exhibited transmural dyskinesis (group 1), whereas 5 had transmural hypokinesis (group 2). In group 1, all layers exhibited comparable degrees of paradoxical systolic thinning during LAD occlusion. After REP, however, recovery was delayed in the inner compared with the mid and outer layers. At 2 h, ThF averaged 34.2 +/- 11.9% of base line in the endocardium vs. 61.7 +/- 16.2% in the midmyocardium and 51.0 +/- 12.3% in the epicardium (F = 4.29, P less than 0.002); similar differences were noted at 3 and 4 h. In the mid and outer layers, ThF returned to base-line values by 24 h, whereas in the inner layer it was still significantly depressed (P less than 0.05) at 24 h (77.3 +/- 5.1% of base line) and recovered by 48 h. The inner-to-outer ThF ratio was decreased (P less than 0.01) for 24 h after REP, indicating maldistribution of thickening in the "stunned" myocardium. In group 2, all layers exhibited hypokinesis during LAD occlusion. Again, recovery of function after REP was delayed in the endocardium compared with the other layers. This study demonstrates that after both severe ischemia resulting in dyskinesis and mild ischemia resulting in hypokinesis, REP is associated with slower recovery of function in the inner than in the outer layers. Thus myocardial "stunning" is a nonuniform phenomenon with maximal severity in the subendocardium.

Animals↗

PubMed1989

Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion. Evidence that myocardial "stunning" is a manifestation of reperfusion injury.

Recent evidence suggests that postischemic myocardial dysfunction ("stunning") may be mediated by oxygen free radicals, but the exact time window during which the critical radical-mediated damage develops remains unknown. Furthermore, the evidence for the oxyradical hypothesis is indirect and, therefore, inconclusive. Thus, the potent and cell-permeable antioxidant N-(2-mercaptopropionyl)-glycine (MPG) was administered as an intra-coronary infusion (8 mg/kg/hr) to three groups of open-chest dogs undergoing a 15-minute coronary occlusion followed by 4 hours of reperfusion. In group I (n = 8), the infusion of MPG was started 15 minutes before occlusion and ended 2 hours after reperfusion; in group II (n = 9), MPG was started 1 minute before reperfusion and ended 2 hours thereafter; in group III (n = 10), MPG was started 1 minute after reperfusion and ended 2 hours and 15 minutes thereafter. Control dogs (group IV) (n = 10) received vehicle. Recovery of contractile function (assessed as systolic wall thickening) was equivalent in groups I and II, and in both groups it was substantially greater than in controls (p less than 0.005 at 4 hours). In contrast, in group III recovery of function was indistinguishable from controls. To determine whether the protection afforded by MPG was due to inhibition of free radical reactions, myocardial production of free radicals was directly assessed by intracoronary infusion of the spin trap alpha-phenyl N-tert-butyl nitrone (PBN). In control dogs (group VII, n = 6), radical adducts of PBN were released in the coronary venous blood after reperfusion, with a burst occurring in the first 5 minutes. MPG given as in group II (group V, n = 5) markedly suppressed myocardial production of PBN adducts (delta = -98% over 3 hours, p less than 0.01 vs. controls); this effect was evident immediately after reperfusion. MPG given as in group III (group VI, n = 5) also suppressed PBN adduct production (delta = -83% over 3 hours, p less than 0.025 vs. controls), but this effect was delayed. Hence, the radicals important in myocardial stunning appear to be those generated immediately after reperfusion. In vitro studies demonstrated that MPG is an exceptionally powerful scavenger of .OH (rate constant = 8.1 x 10(9) M-1 sec-1 by pulse radiolysis) but has no significant effect on .O2- (rate constant less than 10(3) M-1 sec-1), H2O2 (rate constant = 1.6 M-1 sec-1), or non-.OH-initiated lipid peroxidation, suggesting that removal of .OH is the major mechanism of the beneficial effects of MPG.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

Postischemic mechanical and vascular dysfunction (myocardial "stunning" and microvascular "stunning") and the effects of calcium-channel blockers on ischemia/reperfusion injury.

The purpose of this review is to summarize current concepts regarding the sequelae of myocardial ischemia and reperfusion and the effects of calcium-channel blockers. This article will focus on three topics: (1) the phenomenon of postischemic myocardial dysfunction (myocardial "stunning"); (2) the phenomenon of postischemic vascular dysfunction (microvascular "stunning"); (3) the effects of calcium-channel blockers on myocardial ischemia and reperfusion injury.

Animals↗

PubMed1988

Quantification of myocardial infarction during coronary occlusion and myocardial salvage after reperfusion using cardiac imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile.

Myocardial imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile was investigated as a means to assess myocardial infarct size during coronary occlusion and to quantify the extent of salvaged myocardium after coronary occlusion followed by reperfusion. Open chest dogs underwent either a permanent coronary artery occlusion (Group 1, n = 16) or a 2 h occlusion followed by reperfusion (Group 2, n = 15). Animals in both groups were killed 48 h after occlusion. During coronary occlusion, 23 of the 25 dogs that survived the coronary occlusions had abnormal myocardial scintigrams. The scintigraphic perfusion defect size correlated well with the pathologic infarct size (r = 0.85 and 0.95 by planar and tomographic imaging, respectively). The planar scintigraphic defect size, but not the tomographic defect size, overestimated the pathologic size. The planar scintigraphic defect size observed during coronary occlusion was markedly reduced 48 h after reperfusion (24.8 +/- 12.8% to 10.6 +/- 9.7% of the left ventricle, p less than 0.003). The uptake of technetium-99m hexakis 2-methoxyisobutyl isonitrile in the ischemic myocardium increased significantly 48 h after reperfusion (p less than 0.003) and correlated with the increase in regional myocardial blood flow, as assessed by radioactive microspheres (r = 0.83, p less than 0.01). Thus, myocardial imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile allows reliable demonstration of the presence of acute infarction, estimation of infarct size and quantification of the extent of salvaged myocardium after coronary reperfusion.

Animals↗

PubMed1988

Demonstration of free radical generation in "stunned" myocardium of intact dogs with the use of the spin trap alpha-phenyl N-tert-butyl nitrone.

Recent studies suggest that oxygen free radicals may mediate postischemic myocardial dysfunction ("stunning"), but all the evidence for this hypothesis is indirect. Thus, we used electron paramagnetic resonance (EPR) spectroscopy and the spin trap, alpha-phenyl N-tert-butyl nitrone (PBN), to directly investigate whether free radicals are produced after a 15-min coronary artery occlusion and subsequent reperfusion in 30 open-chest dogs. After intracoronary infusion of PBN, EPR signals characteristic of oxygen- and carbon-centered radical adducts were detected in the venous blood draining from the ischemic/reperfused vascular bed. The myocardial release of PBN adducts began during coronary occlusion but increased dramatically in the first few minutes after reperfusion. After this initial burst, the production of radicals abated but did not cease, persisting up to 3 h after reflow. The EPR spectra (aH beta = 2.67-2.79 G, aN = 14.75-15.00 G) were consistent with the trapping by PBN of secondary oxygen- and carbon-centered radicals, such as alkoxy and alkyl radicals, which could be formed by reactions of primary oxygen radicals with membrane lipids. There was a linear, direct relationship between the magnitude of PBN adduct production and the degree of ischemic flow reduction. Recovery of contractile function (measured as systolic wall thickening) after reperfusion was greater (P less than 0.05) in dogs given PBN than in controls. This study demonstrates that reversible regional myocardial ischemia in the intact animal is associated with prolonged free radical generation, and that the intensity of such generation is related to the severity of ischemia. The results provide direct evidence to support the hypothesis that reactive oxygen metabolites contribute to the persistent contractile dysfunction (myocardial stunning) observed after brief ischemia in vivo.

Animals↗

PubMed1987

Brucella endocarditis.

Brucella endocarditis is an underdiagnosed, fatal complication of human brucellosis. Four successfully treated cases of Brucella endocarditis are reported. The development of a new valvar lesion and bulky vegetations seen on echocardiography helped to identify Brucella endocarditis occurring during systemic brucellosis. The aortic valve was affected in all four patients, and in one the mitral valve was also affected. Medical treatment did not cure the patients and all needed valve replacement--for haemodynamic deterioration in three and because a further embolism was feared in one. Antibiotics were continued for six to nine months after operation. There was no early or late mortality and no recurrence after a follow up of 15 months.

Adult↗