Ischemic heart disease as deficiency disease.

Four classes of agents capable of producing human illness have been identified: toxicity, heredity, infection and deficiency. The leading paradigm for the etiology and pathophysiology of ischemic heart disease in the 20th century was that of intoxication by too much of the wrong kind of dietary fat. This overemphasis on lipid metabolism persists because important data are neglected and because of inattention to details. For example, heart disease risk does not correlate with fat intake within nations in contrast to between nations. Also development of ischemic heart disease involves inter alia arterial spasm, cardiac rhythm, metabolism of connective tissue, glucose and homocysteine, plus paraoxonase activity and thrombus formation which generally are unaffected by dietary fat. Homocysteine thiolactone accumulates when homocysteine is high. This lactone specifically inhibits lysyl oxidase which depends on copper to catalyze cross linking of collagen and elastin in arteries and bone. The lactone is hydrolyzed by paraoxonase, activity of which can be decreased by copper deficiency. Just as cholesterol was an important focus for heart disease as intoxication, homocysteine can become an excellent focus for a paradigm shift to heart disease as deficiency because supplementation with several nutrients can alter homocysteine metabolism and decrease its plasma concentration. These supplements include betaine, copper, folate, pyridoxine and vitamin B-12. Opportunities for research on ischemic heart disease as deficiency disease are plentiful.     

Epidural morphine for outpatients with severe anginal pain.

Seven patients who had chronic coronary artery disease and had undergone coronary artery bypass surgery still suffered from anginal attacks several times daily despite optimal medical treatment. An epidural system of analgesia was implanted subcutaneously and treatment with epidural morphine started. The morphine was administered by the patients themselves or members of their family. During a median observation time of four months (range three to 11) all patients were free of pain while receiving this treatment.     

Letter: Ischemic heart disease,water hardness and myocardial magnesium.

In 54 cases of accidental death in cities with water hardness of 60 parts per million (ppm) or less, the mean myocardial magnesium concentration was 918 mug/g of dry tissue. This was 7% lower than the corresponding figure of 982 mug/g among 29 cases of accidental death in cities with water hardness of 300 ppm or more, and this difference was significant (P less than 0.01). There were no significant differences between the cities with soft and hard water in the mean myocardial concentrations of calcium, zinc, copper, chromium, lead or cadmium. These results are compatible with the belief that the relatively high death rates in some soft-water areas may be due to a suboptimal intake of magnesium, and that water-borne magnesium exerts a protective effect on the residents of hard-water areas.     

Ischemic bowel disease

The clinical, radiologic and pathologic features of 25 cases of ischemic bowel disease are presented. The majority of patients presented with the triad of abdominal pain, diarrhea and vomiting. In 13 patients the diarrhea was associated with the passage of bright red blood per rectum. There were 10 cases of infarction, 11 of enterocolitis and 4 had resulted in stricture formation. In five cases of enterocolitis the lesion was transient; symptoms improved with conservative medical management and the radiologic findings returned to normal. Barium enema examination yielded abnormal findings in the majority of the cases in which it was performed. Plain films of the abdomen, however, were not helpful. The actual mortality in this group of patients was 44%, 80% in those with infarction of the bowel and 20% in the other two groups.     

Ischemic preconditioning in isolated perfused mouse heart: Reduction in infarct size without improvement of post-ischemic ventricular function

Genetically engineered mice provide an excellent tool to study the role of a particular gene in biological systems and will be increasingly used as models to understand the signal transduction mechanisms involved in ischemic preconditioning (IP). However, the phenomenon of IP has not been well characterized in this species. We therefore attempted to examine whether IP could protect isolated mouse heart against global ischemia/reperfusion (GI/R) injury. Thirty adult mice hearts were perfused at constant pressure of 55 mmHg in Langendorff mode. Following 20 min equilibration, the hearts were randomized into three groups (n = 10/each): (1) Control Group; (2) IP2.5 Group: IP with two cycles of 2.5 min GI + 2.5 min R; (3) IP5 Group: IP with 5 min GI + 5 min R. All hearts were then subjected to 20 min of GI and 30 min R (37°C). Ventricular developed force was measured by a force transducer attached to the apex. Leakage of CK and LDH was measured in coronary efflux. Infarct size was determined by tetrazolium staining. Following sustained GI/R, infarct size was significantly reduced in IP2.5 (13.8 ± 2.3%), but not in IP5 (20.1 ± 4.0%), when compared with non-preconditioned control (23.6 ± 3.8%) hearts. CK and LDH release was also reduced in both IP2.5 and IP5 groups. No significant improvement in post-ischemic ventricular contractile function was observed in either IP groups. We conclude that IP with repetitive cycles of brief GI/R is able to reduce myocardial infarct size and intracellular enzyme leakage caused by a sustained GI/R in the isolated perfused mouse heart. This anti-necrosis cardioprotection induced by IP was not associated with the amelioration of post-ischemic ventricular dysfunction.     

Direct coronary arterial stenting without predilatation in patients with coronary heart disease

The study was undertaken to evaluate the safety and efficiency of direct stenting versus routine stenting with predilation. It included 133 patients. By the decision of operators, direct stenting was conducted in 66 patients (71 stenoses) (Group 1). The remaining 67 patients (73 stenoses) underwent routine stenting with predilation (Group 2). The initial angiographic success of stenting was 100% in Group 1 and 98 in Group 2. Complications were absent. In the direct stenting group, technical problems occurred during a session in 9 (12%) cases. In this group the mean duration of fluoroscopy and the total duration of a session were much less than in the routine stenting group. The mean number of balloons used at dilation per stenosis and the number of dilation sessions per stenosis were much lower in Group 1 than in Group 2. The results of quantitative angiogram analysis before and after a session were similar in both patient groups. Six months following stenting, angiographic restenosis occurred in 7 (10%) patients in Group 1 and in 9 (12%) in Group 2. Direct stenting is a safe and effective treatment for non-occlusive coronary lesions without marked kinks and calcinosis. Direct stenting reduces the duration of fluoroscopy and the total duration of an operation by 50 and 22%, respectively, as compared to predilation stenting.