Cardiac conduction abnormalities have been reported in families with Leber's hereditary optic neuropathy (LHON). The pre‐excitation syndrome, Wolff‐Parkinson‐White syndrome or Lown‐Ganong‐Levine syndrome, is reportedly common in Finns with LHON, being seen in 14 (9%) of the 163 individuals with mitochondrial DNA (mtDNA) mutations. While this syndrome is thought to be rare in other ethnic groups with LHON, the present study of 35 Japanese LHON families confirmed that it is also relatively common among Japanese families, being seen in 5 (8%) of the 63 individuals with mtDNA mutations. It remains to be determined whether the high incidence of the pre‐excitation syndrome in Finnish and Japanese LHON families is due to a particular genetic composition of ethnic groups such as in Finland and in Japan, or only to a reporting bias.
Background Although both clinical and animal studies have shown that ischemic tolerance is reduced in the senescent myocardium, it has not been clarified when myocardium becomes more vulnerable to ischemia. Preconditioning protects the hearts of young adult animals of various species, but its effects are not identical in human studies. We investigated whether ischemic tolerance and the effect of preconditioning decreased in isolated hearts of middle-aged rats. Methods and Results The hearts of young adult rats (12 weeks old: group Y, n=44) and middle-aged rats (50 weeks old: group M, n=44) were subjected to global ischemia for 15, 20, or 25 minutes followed by reperfusion. Hearts were also subjected to preconditioning and then to 20 (group Y, n=22) or 15 (group M, n=22) minutes of ischemia followed by reperfusion. Left ventricular developed pressure (LVDP) was decreased by 40% to 60%, and the level of ATP was decreased by 60% to 70% in group M compared with group Y. Preconditioning increased LVDP (% LVDP, 40.5% to 72.4%) and levels of high-energy phosphates (ATP, 11.8 to 14.1; creatine phosphate, 17.0 to 23.1 μmol/g dry wt) and reduced left ventricular end-diastolic pressure (LVEDP, 32.8 to 10.3 mm Hg), creatine kinase release (257 to 132 U/g dry wt), and ryanodine-sensitive sarcoplasmic reticulum Ca 2+ release after ischemia in group Y. Preconditioning exerted opposite effects in group M (% LVDP, 45.9% to 15.8%; LVEDP, 21.0 to 28.5 mm Hg; ATP, 14.1 to 8.5 μmol/g dry wt; and CK release, 176 to 332 U/g dry wt). Preconditioning was associated with increases in the incidence of reperfusion-induced ventricular fibrillation (0% to 62.5%) and the rate of sarcoplasmic reticulum Ca 2+ release in group M. Conclusions These results indicate that hearts became more vulnerable to ischemia with age and that the beneficial effects of preconditioning were reversed in middle-aged rat hearts.
The delayed outward rectifier K+ channel has a role in the increase in automaticity of myocytes under pathophysiological conditions. The purpose of the present study was to clarify the effect of blockade of outward recitifier K+ channels by a class III antiarrhythmic drug, E4031, on ischemia- and reperfusion-induced arrhythmias. Ion fluxes, energy metabolites and cardiac function were measured and the epicardial electrocardiograms of Langendorffperfused rat hearts were recorded during initial perfusion, global or regional ischemia and reperfusion. 10-7M of E4031 administered during the initial perfusion did not prolong the QT interval, but slowed the heart rate (Control: 222, E4031: 183bpm, p<0.05), increased myocardial 45Ca2+ uptake (Control: 2.1, E4031: 2.9μmol/g dwt, p<0.05) and attenuated the loss of intracellular K+ during ischemia (Control: 238, E4031: 248μmol/g dwt, p<0.05). E4031 tended to reduce ischemia-induced ventricular tachyarrhythmias (Control: 60, E4031: 30%, n. s.), but reperfusion-induced ventricular tachyarrhythmias were sustained longer by the administration of E4031 (Control: 255, E4031: 623sec, p<0.05). Prior exposure to E4031 decreased the depletion of high energy phosphates during ischemia, but suppressed their recovery during reperfusion. These results suggest that the attenuated loss of K+ from the ischemic myocardium and the decrease in heart rate by E4031 contributed to the reduction of ischemia-induced arrhythmias. However, the increase in myocardial Ca2+ uptake and altered energy metabolism may be responsible for the increase in reperfusion-induced arrhythmias.(Jpn HeartJ 1998; 39: 183-197)
A number of studies have been published which have attempted to define the electrocardiographic (ECG) changes with aging, but most of them were obtained from cross-sectional studies. To distinguish ECG changes related to physiological aging from those associated with arteriosclerosis, we assessed the ECG changes of 500 apparently healthy subjects, aged 60 years and older in 1992, who had been followed at the Keio Health Consulting Center for over 15 years. All subjects had no overt cardiovascular diseases in 1992. We compared the ECG in 1992 with that taken over 15 years ago. Changes in ECG during that period were also reviewed. With aging, the mean axis deviated to the left, the mean QTc interval was shortened, and the mean PR interval was prolonged. ST segmental change, atrial overloading, bundle branch block developed newly in 16%, 8% and 7% of, respectively. There were no relationships among axis deviation, PR interval change, or QTc shortening and coronary risk factors. QTc prolongation and ST segmental change were strongly related to hypertension or impaired glucose tolerance. When ECG changes in those under 65 years old were compared with those over 80 years old, the incidence of ST segmental change in those over 80 years old was significant higher. This study was not a prospective study but suggested each type of ECG change related to aging was affected by physiological and/or pathological factors in a distinct way and had different phases of development and progression.
To clarify the roles of subclasses of α1-adrenoreceptors in ischemic-reperfused myocardium, we compared the effect of the nonselective α1-blocker bunazosin with that of the α1A-blocker WB4101 and the α1B-blocker chlorethylclonidine (CEC) in isolated rat hearts. After 30 min of preperfusion, Langendorff-perfused hearts were subjected to 25 min of global ischemia followed by 30 min of reperfusion. Hearts were randomly divided into 4 groups, with one of the following substances being added to the perfusate: buffer alone (control), 10-6 mol/L bunazosin, 10-7 mol/L WB4101, or 10-7 mol/L CEC. Bunazosin had a negative inotropic effect and preserved the postischemic ATP content, reduced the postischemic increase in intracellular Na+ content and then enhanced postreperfusion recovery of creatine phosphate. Bunazosin also reduced myocardial 45Ca2+ uptake during reperfusion (control 5.2 vs bunazosin 2.5 μmol/g dry weight of tissue (dwt), p<0.01). However, the recovery of left ventricular developed pressure (DP) was not improved when bunazosin was added to the perfusate during reperfusion. WB4101 had neither a negative inotropic nor an energy-sparing effect, but it improved the recovery of DP (control 43% vs WB4101 56% of preischemic value, p<0.05) with no reduction in myocardial 45Ca2+ uptake. CEC had a negative inotropic and energy-sparing effect and then reduced myocardial 45Ca2+ uptake (CEC 3.1 μmol/g dwt, p<0.05), but it did not improve the recovery of DP. These results suggest that the preischemic administration of an α1B-adrenoreceptor subtype blocker protected ischemic-reperfused myocardium via reduction of Ca2+ overload, whereas the selective blockade of the α1A-adrenoreceptor subtype reduced myocardial damage via mechanism(s) other than Ca2+ metabolism. (Jpn Circ J 1997; 61: 927 - 935)
