Using transient entrainment. the effect of the paced cycle length on the conduction through the reentrant circuit was assessed in recurrent sustained ventricular tachycardia (VT). Fourteen patients were included in the present study and their VTs Were paced at multiple cycle lengths while the criteria of entrainment were confirmed at each paced cycle length. Then. the effect of the paced cycle length upon the conduction time. which was evaluated by the measurement of the time interval from stimulus to the entrained electrogram. was analyzed. In the overdrive pacings of VT, 3 response patterns in conduction time were observed: an increasing pattern (n=8), a flat pattern (n=5) and a decreasing pattern (n=1) while the local conduction time outside the reentrant circuit remained unchanged at comparable paced cycle lengths. A decremental property is the likely mechanism responsible for the paced cycle length-dependent prolongation. As for the flat pattern, the existence of a fully excitable gap may be responsible. A paced cycle length related change in the reentrant circuit may account for the decreasing pattern. By using transient entrainment. the electrophysiological characteristics of the reentrant circuit can be evaluated and the information so gathered may be valuable in analyzing the action of antiarrhythmic drugs on the slow pathway.

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We performed 12-lead electrocardiography (ECG) repeatedly in 13 patients with cardiac transplants. QRS block occurred at some point in 12 patients and its course was either sporadic. progressive. persistent or fluctuating (5, 3, 3 and 1 patient (s). respectively). In the first postoperative week, complete or incomplete right bundle branch block (RBBB) occurred in 10 patients. Left anterior fascicular block also occurred in 3 of the 10 patients. However, the block (s) subsided within 1 month in the 3 and 2 more patients. Nonspecific block. isolated left anterior fascicular block and left bundle branch block also occurred occasionally. QRS block was unrelated to the occurrence of cardiac rejection. catheter injury, right ventricular pressure or volume overloading, left ventricular function. and the length of ischemic time of the donor heart. Two patients have had permanent RBBB since the immediate postoperative period despite a normal donor electrocardiogram before harvesting. The temporal courses of QRS block varied widely in 9 patients. Thus. different mechanisms may have been active in various postoperative periods. The occurrence of QRS block was unrelated to morbidity and mortality in the recipients. Therefore, longer observation will likely establish the benign nature of the QRS block in this disease.

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The square root (dip and plateau) sign was observed in 7 of 21 adult patients with atrial septal defect (ASD). This study evaluated left ventricular (LV) diastolic filling dynamics and hemodynamic findings in 7 patients (Group 1) with, and 14 patients (Group 2) without the square root sign; 10 normal subjects (Group 3) served as controls. No significant differences were observed in LV end-diastolic and end-systolic volumes, ejection fraction, or left to right shunt. In Group 1, 77% of LV filling was completed in the first half of diastole; this percentage was 49% and 53% in Groups 2 and 3, respectively (both p<0.01 versus Group l). Early diastolic filling velocity (at 20% of diastole) in Group 1 was significantly greater, and late diastolic filling velocity (at 80% and 90% of diastole) was reduced in Group 1 compared to those in Groups 2 and 3 (all p<0.05). The average values for right and left ventricular end-diastolic press-ures were sigrrificantly higher in Group I (11±2 and l0±4 mmHg, p<0.05) than Group 2 (7±2 and 7±2 mmHg, p<0.05). It is suggested that a constrictive pathophysiology due to 4 chambers interaction or right ventricular constraint may play a role in the genesis of the square root sign in ASD.

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This study aimed to examine the dynamic changes of the fibrinolytic system during coronary vasospasm. Tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI) and fibrinopeptide A (FPA) levels were measured in the great cardiac venous and arterial blood of 9 patients with clinically and angiographically proven vasospastic angina and 11 controls. Before ergonovine provocation, although there was no difference between the above 2 groups in t-PA levels in the aorta or the great cardiac vein, the PAI level in patients with variant angina was lower than in the controls both in the aorta (4.2±3.5 IU/ml vs 10.9±5.2 IU/ml) and in the great cardiac vein (2.3±2.9 IU/ml vs 11.9±4.9 IU/ml). During ergonovine-induced coronary vasospasm in patients with variant angina, the t-PA level in the great cardiac vein significantly increased from 3.4±0.7 ng/ml to 4.4±0.5 ng/ml (p<0.05), but it did not change in the aorta. The maximal dose of ergonovine (0.4mg) induced mild diffuse coronary vasoconstriction in the controls, and this diffuse coronary vasoconstriction induced a reduction of PAI levels in the great cardiac vein from 11.9±4.9 IU/ml to 9.5±4.8 IU/ml (p<0.05). FPA levels in the great cardiac vein did not change during ergonovine-induced coronary vasospasm in either group. Thus, the coronary vasospasm induced the release of t-PA from endothelial cells of coronary vessels and resulted in the reduction in the PAI activity in the great cardiac vein. In conclusion, during coronary vasospasm, the fibrinolytic system seems to play an anti-thrombogenic role in coronary arteries.

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To investigate the causative factors of dilated cardiomyopathy (DCM). 29 DCM patients were echocardiographically and histopathologically compared with 17 patients with specific heart muscle diseases mimicking DCM. These consisted of 6 cases of myocarditis and 11 of alcoholic heart muscle disease. Myocarditis patients had less dilation of the left ventricle, more marked segmental wall motion abnormality on admission and more extensive myocardial fibrosis than patients with alcoholic heart muscle disease and DCM. Four myocarditis patients died of, congestive heart failure before showing a marked dilalation of the left ventricle. The alcoholic heart muscle disease patients revealed diffuse wall motion abnormality on admission. Out of these 8 patients who had abstained showed amelioration. However, in 3 who had not abstained, both wall motion abnormality and dilatation of the left ventricle markedly progressed and 2 died of congestive heart failure. Although the DCM patients as a group showed deterioration throughout the follow-up period, individual patients revealed a variety of echocardiographic and pathological findings, which led to the regrouping of 29 patients with DCM into 2 subgroups. One group had characteristic features similar to these of patients with myocarditis, and the other had characteristics similar to these of patients with alcoholic heart muscle disease. These findings suggested that different causative factors might coexist in DCM.

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The heart as the primary site of lesion in malignant lymphoma is extremely rare. We experienced 2 cases of malignant lymphoma whose initial presentation was massive pericardial effusion with cardiac tamponade. The first case was a 75-year-old man who had shortness of breath for 1 week. Chest X-ray showed cardiomegaly (CTR 65%), and his condition was diagnosed as congestive heart failure at first and thereafter echocardiogram revealed pericardial effusion. The second case was a 76-year-old man who complained of exertional dyspnea which worsened over 2 weeks. His condition was diagnosed as congestive heart failure at first and echocardiogram revealed pericardial effusion. Pericardial drainage tapped bloody fluid and cytological examination revealed malignant lymphoma. After treatment. the first case lived for eleven months with no recurrence of pericardial effusion. The second case has lived for 4 years. We present these 2 cases can be defined as primary cardiac lymphoma according to MCALLISTER and FENOGLIO. i.e.. a lymphoma that involves only the heart and pericardium. More cases of primary cardiac lymphoma will be found in the future because of the ease with which the echocardiogram can detect pericardial effusion.

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In a previous study, we proved experimentally that transmural infarction was produced in the area of the left anterior descending artery (LAD) by coronary sinus occlusion attributable to thrombus formation. In an attempt to produce infarction due to thrombus formation and to investigate the influence of thrombosis. the anterior interventricular vein (AIV) was occluded in this study. In each of 6 adult mongrel dogs, a balloon-tipped catheter was wedged in the AIV via the jugular vein. After the occlusion of blood flow by inflation of the balloon. thrombin (30-50 IU) was injected into the AIV to produce thrombi and the balloon was removed 60 min later. As a result, ischemic changes of ST and T in an ECG were clearly observed in all 6 dogs, and serum levels of myocardial enzymes supported the development of myocardial necrosis. Coronary arteriography performed 48 hours after the occlusion of the AIV showed normal findings in all 6 dogs, and residual thrombi in the AIV were observed in 5 dogs by coronary venography. In these 5 dogs. very local contranction band necrosis (CBN) was noted in the epicardium surrounding the AIV. These experimental findings indicate the following: 1) CBN can also be induced by corocary venous occlusion. 2) once the occlusive mechanism acts on the coronary venous system. the changes which are clinically similar to myocardial infarction can be induced regardless of its causes. 3) ischemic changes in myocardium can be localized in the epicardium irrespective of its causes. Therefore, these findings are considered to be important in the investigation of the clinical onset mechanism of myocardial infarction.

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We developed a simple procedure to detect the interaction of muscarinic receptors in atrial membranes with exogenous GTP-binding proteins (G proteins). The procedure consists of mixing atrial membranes with G proteins in the presence of sodium cholate, diluting the mixture with a salt buffer and then measuring the ligand binding activity. The displacement by carbachol of [³H] QNB binding to muscarinic receptors in the atrial membranes was not affected by guanine nucleotides when the membranes had been treated at 60°C for 30 min or with N-ethylmeleimide (NEM) and became affected by them after mixing the heat- or NEM-treated membranes with G proteins. The displacement curves in the presence of GTP were essentially the same irrespective of the presence or absence of G proteins. Those in the absence of GTP shifted to a lower concentration of, carbachol with addition of a higher concentration of G proteins, indicating an increase in GTP-sensitive high affinity agonist binding sites. The highest affinity for carbachol was detected with membranes treated with NEM and then mixed with G proteins. The GTP-sensitive high affinity agonist binding could be detected with any one of three kinds of G proteins (Gi, Go, Gn) which were purified from porcine cerebrum, indicating that the muscarinic receptor m2 subtype may interact with and possibly activate these three kinds of G proteins.

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Cardiac sarcoplasmic reticulum (SR) plays a special role in controlling free calcium ions (Ca) in heart muscle cells. Ca stored in the SR is released through the Ca release channels when the sarcolemmal membrane is depolarized, thereby inducing contraction, while Ca is reaccumulated by the Ca pump to induce relaxation. In the latter process, the Ca pump of cardiac SR has a regulatory system by cAMP-dependent phosphorylation of a SR protein, phospholamban, Recently, significant progress has been achieved in understanding the molecular mechanisms of Ca release and uptake and its regulation. The structures of the Ca pump and phospholamban have been defined at molecular levels. A direct interaction between these two proteins was demonstrated. The Ca release channel was identified, and turned out to be the foot structure which in situ connects the SR to the sarcolemma/transverse tubule.

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Cardiac hypertrophy is associated with qualitative as well as quantitative changes in myocardial cells. To analyze the molecular basis of isozymic transitions of cardiac myosins in response to pressure overload, we have constructed and characterized two types of myosin heavy chain (MHC) cDNA clones, specifying α- and β-MHCSs, and two types of myosin alkali light chain cDNA clones. complementary to atrial type (ALC1) and ventricular, type (VLC1) mRNAs from a human fetal heart cDNA library. Using the S1 nuclease mapping procedure, we showed that the MHC isozymic transitions from α- to β-MHC in the pressure overloaded atria are produced by changes in the relative level of α- and β-MHC gene expression. In addition, we observed that the expression of VLC1 gene is also induced in the atria subjected to severe pressure overload. Thus, it appears that the increased expression of VLC1 gene. together with the isogene switch from α- to β-MHC gene, may participate in the adaptation of myocardium to new functional requirement. Then, to get a better understanding of the genetic mechanisms involved in the regulation of isogene expression, we have isolated and sequenced genomic clone for VLC1 isoform. Sequence analysis has identified multiple potential cis regulatory elements within a 686-bp upstream region. This region includes 28-bp alternating purine/pyrimidine sequences and two segment exhibiting homology to consensus sequence proposed for viral and cellular enhancer elements. In particular, a comparison of the VLC1 upstream gene sequence with those available for sevaral muscle-specific genes revealed that CC(A + T-rich)₆GG elements and CATTCCT sequence are conserved. These results suggested that CArG box (-96 to -87) has an important role in the positive regulation of the VLC1 gene and this element may be involved in the co-regulation of VLC1 and cardiac α-actin genes.

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α- and β- human cardiac myosin heavy-chain (MHC) genes, which correspond to MYH6 and MYH7, respectively, according to Human Gene Mapping nomenclature, were isolated from human genomic and cDNA clones, using two rat cardiac pCMHC26: α-MHC type; and pCMHC5: β-MHC type as probes, and characterized. The α-MHC type cardiac genomic DNA clone and the β-MHC type cardiac cDNA clone were used as probes in the Southern analysis of human genomic DNA from human-Chinese hamster or human-mouse somatic cell hybrids. The results showed that the human cardiac MHC gene is assigned to chromosome 14 and the human cardiac and skeletal MHC genes do not cosegregate as do the mouse cardiac and skeletal MHC genes. For further analysis, a regional mapping method was used. DNA from 4 human deletion and 3 human duplication cell line were prepared for southern blotting, hybridized with human cardiac α- and β-MHC DNA probes. and the hybridization intensity relative to 46, XX or 46, XY DNA was estimated. The results showed that two human cardiac MHC genes segregated with the 14cen-ql3 region of the long arm of human chromosome 14. In situ hybridization of ³H-labeled human cardiac α-MHC probe to normal human metaphase chromosome independently confirmed this result.

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Endothelin (ET) is a potent vasoconstrictor peptide produced by vascular endothelial cells. Three distinct human endothelin genes were cloned and analysed. The results demonstrated that there were three distinct mRNAs for ET and that TPA-responsive element, mRNA stabilizing sequence, motifs for binding site of nuclear factor 1 and acute phase reactant regulatory elements were recognized in preproform ET-1 gene.

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