Hitoshi Ooiwa

Clinical implications of midventricular obstruction and intravenous propranolol use in transient left ventricular apical ballooning (Tako-tsubo cardiomyopathy)

BACKGROUND Persistent hypotension with dynamic midventricular obstruction (MVO) in patients with transient left ventricular (LV) apical ballooning (Tako-tsubo cardiomyopathy) is an important complication that needs to be treated. PURPOSE The objective of this study is to determine the effects of intravenous propranolol challenge on MVO in transient LV apical ballooning. SUBJECTS AND METHODS Thirty-four patients (12 males, 22 females, mean age 64 +/- 17 years, age range 22-84 years) with LV apical ballooning were enrolled. The hemodynamic and echocardiographic effects of propranolol (0.05 mg/kg, maximum 4 mg) were analyzed in 13 patients. RESULTS (1) Midventricular obstruction was present in 8 (24%) of 34 patients, and the pressure gradient (PG) ranged from 28 to 140 mm Hg. (2) Patients with MVO had similar demographic and clinical characteristics (symptoms, peak creatine kinase, plasma catecholamine levels) as those without MVO; however, in patients with MVO, abnormal Q waves on electrocardiogram and hypotension were more prevalent. (3) In the MVO group, intravenous propranolol changed the PG from 90 +/- 42 to 22 +/- 9 mm Hg, the systolic blood pressure (SBP) from 85 +/- 11 to 116 +/- 20 mm Hg, and the LV ejection fraction (LVEF) from 30% +/- 7% to 43% +/- 4%. (4) In all subjects, the changes in the PG after propranolol injection had a significant linear correlation with the SBP and LVEF changes: deltaSBP = 4.738 + 0.315 x deltaPG (r = 0.689 (P < .001) and deltaLVEF = 2.973 + 0.1321 x deltaPG (r = 0.715, P < .001). CONCLUSION Intravenous propranolol is useful for treating dynamic MVO in patients with transient LV apical ballooning.

Tetrazolium artifactually indicates superoxide dismutase-induced salvage in reperfused rabbit heart

We tested the ability of a single dose of superoxide dismutase to induce salvage of reperfused rabbit myocardium. Infarct size was measured by tetrazolium method following 3, 24, or 72 h of reperfusion. In addition, the 24 h reperfused hearts were examined to determine if the drug induced salvage in those hearts was reflected in the histology. A coronary arterial branch was occluded for 45 min and then allowed to reperfuse for 3, 24 or 72 h. At the end of the reperfusion period the hearts were removed, perfusion stained with triphenyl tetrazolium, and fixed in buffered formalin. The hearts were sectioned and infarct size was determined in all groups. In addition, the 24 h heart slices were prepared for histology with H&E staining. The results revealed that 5 mg/kg hSOD treatment was associated with smaller infarcts in the 3 and 24 h groups but that differences were no longer apparent in the 72 h group. The 24 h control hearts showed good correlation between infarct size by TTC and that by conventional histology. In the 24 h treatment hearts, however, infarcts by TTC averaged only about 1/2 the size of those by conventional histology. We conclude that a single dose of hSOD fails to offer a sustained reduction of infarct size. Furthermore, histology from the 24 h reperfused group revealed that hSOD did not delay the onset of necrosis but rather simply caused dead tissue to retain its ability to reduce the tetrazolium salts.

Superoxide dismutase conjugated to polyethylene glycol fails to limit myocardial infarct size after 30 min ischemia followed by 72h of reperfusion in the rabbit

We tested whether recombinant human superoxide dismutase conjugated to polyethylene glycol (PEG-SOD) to prolong its plasma retention time could limit myocardial infarct size in an ischemia-reperfusion model in the rabbit. One group of animals received 1000 units/kg of PEG-SOD as an intravenous bolus 15 min before coronary occlusion. A second group received saline only and served as controls. Under pentobarbital anesthesia, a left coronary branch was occluded for 30 min and then reperfused. The surgical wounds were repaired and the animals were allowed to recover. Seventy-two hours after the coronary occlusion, the heart was excised and the size of the area at risk (ischemic vascular bed) was assessed with fluorescent particles and the infarct size was determined by histology (Hematoxylin-eosin, Azan stain). Infarct size as a percentage of the area at risk was similar between the groups, 46.5 + 2.7 in the PEG-SOD group (n = 8) and 48.9 + 3.1 in the control group (n = 8). There were no significant differences between the groups indicating that PEG-SOD did not limit infarct size in this model.

Examination of two small-molecule antiperoxidative agents in a rabbit model of postischemic myocardial infarction

Summary: Peroxidation of membrane phospholipid may be a causal contributor to the development of irreversible postischemic myocardial injury. In this study, two small-molecule antiperoxidative agents were tested for their ability to salvage reperfused rabbit myocardium and reduce infarct size as assessed by direct histological evaluation of hearts following a 30-min occlusion of a coronary arterial branch and a 72-h reperfusion period. The compounds tested are novel analogs of α-tocopherol (vitamin E), and share with the parent compound an ability to scavenge the peroxyl radicals that propagate and amplify lipid peroxidation initiated by partially reduced oxygen; however, the new analogs are significantly more potent peroxyl-radical scavengers than α-tocopherol. Each antiperoxidant (3 mg/kg) was administered by intravenous bolus injection in two stages: 20% of the total dose was given 15 min before occlusion, and the remaining 80% was given 5 min before reperfusion. The results revealed that neither antiperoxidant offered a sustained reduction in infarct size (expressed as a percentage of the region at risk) as compared to a nontreated vehicle control. The implications of the present study with respect to the purported cardioprotective effects of antiperoxidants in the setting of ischemia reperfusion and the pathogenic role of lipid peroxidation in the postischemic heart are discussed.

SUPEROXIDE DISMUTASE ATTENUATED POST‐ISCHAEMIC CONTRACTILE DYSFUNCTION IN A MYOCARDIAL XANTHINE OXIDASE DEFICIENT SPECIES

1. We assessed the effect of polyethylene glycol conjugated superoxide dismutase (PEG‐SOD) on myocardial stunning in the rabbit heart in which xanthine oxidase level is extremely low.

Does verapamil limit myocardial infarct size in a heart deficient in xanthine oxidase

1. The delay of ischaemic myocardial necrosis by verapamil has been reported in the dog heart, which contains a high level of xanthine oxidase, a potential source of cytotoxic free radicals. To test whether the retardation of ischaemic myocyte death by verapamil is not an isolated phenomenon in the xanthine oxidase rich heart, we assessed the effect of verapamil in the rabbit heart, which lacks xanthine oxidase.

Aortic valve aneurysm responsible for acute congestive heart failure and histological findings: A case report

We experienced a case of acute congestive heart failure in a 73-year-old man who had been followed up due to mild-to-moderate aortic stenosis and moderate-to-severe aortic regurgitation. A huge aortic valve aneurysm was found to extend from his right coronary cusp to a left ventricular outflow tract, resulting in moderate subaortic obstruction and severe aortic regurgitation. Surgical repair was performed and a perforated aneurysm of right aortic cusp was identified. Histological examinations suggested that healed infective endocarditis was responsible for the formation of an aneurysm in the aortic valve. <Learning objective: Aortic valve aneurysm is an uncommon complication of infective endocarditis. The infective process of a cardiac valve is thought to augment valvular tissue injury, resulting in aneurysmal formation and perforation of the valvular aneurysm. We report an uncommon case of aortic valve aneurysm that was histologically suggested to be caused by subclinical infective endocarditis. The subaortic obstruction and aortic regurgitation were successfully treated using a surgical procedure.>.