Physiological and pharmacological interventions are used to regulate cardiac contractile functions via modulation of Ca²⁺ signaling. The relevant regulatory mechanisms have recently been assessed in detail by use of novel experimental procedures, which include simultaneous measurements of intracellular levels of Ca²⁺ ions and contractile force in intact myocardial preparations loaded with the intracellular Ca²⁺ indicator aequorin and fluorescent dyes, namely, fura-2, indo-1 and fluo-3. Association with or dissociation from intracellular Ca²⁺ transients of contractile activity is taken as evidence that reflects the primary mechanism of action of individual inotropic interventions. In addition, motility assays of actin-myosin interactions in vitro have made it possible to define the site of action of Ca²⁺ sensitizers as troponin C and the interaction of the troponin-tropomyosin complex with actin or the actin-myosin interface at crossbridges. Frank-Starling mechanism operates at the level of the binding of Ca²⁺ ions to troponin C and subsequent regulatory processes, while the forcefrequency relationship is mainly ascribed to an alteration in the intracellular mobilization of Ca²⁺ ions. Cardiotonic agents can be classified as follows: 1) agents that act via a cyclic AMP-dependent or a cyclic AMP-independent mechanism; and 2) agents that facilitate the intracellular mobilization of Ca²⁺ ions or increase in myofibrillar sensitivity to Ca²⁺ ions. Regulatory mechanisms mediated via the phosphorylation of functional proteins induced by cyclic AMP, which is responsible for the actions of novel cardiotonic agents, β₁-adrenoceptor partial agonist and selective inhibitors of phosphodiesterase (PDE) III, have currently been clarified in more detail. Ca²⁺ sensitizers are of extreme therapeutic interest because of their ability to increase myocardial contractility without an increase in activation energy; they are devoid of risks of arrhythmogenicity and myocardial cell death from intracellular Ca²⁺ overload; and they effectively reverse contractile dysfunction under pathophysiological situations, such as acidosis or myocardial stunning.

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In this prospective randomized trial we explored the possibility of different procedural outcomes with regard to compliant (polyolefin copolymer (POC)), and non-compliant (polyethylene terapthelate (PET)) balloon materials commonly used during percutaneous transluminal coronary angioplasty (PTCA).
For this purpose, 51 female and 149 male (total 200) patients were randomized to 100 compliant and 100 non-compliant balloons. Only single lesions were included in the study and patients who had PTCA for more than one lesion in different segments at different sessions were each entered seperately (there were actually 49 female and 143 male patients). PTCA procedures were performed in conjuction with quantitative coronary angiographic techniques and the films were reviewed by two investigators in a blinded fashion. Statistical analysis for various procedural end-points were performed by non-paired Student t test with statistical significance being p<0.05.
There were no differences in demographic and clinical characteristics between groups. Lesion characteristics of both groups were exactly matching for vessel size, balloon size, balloon vessel ratio, minimal luminal diameter and percent stenosis of the index lesion.
Similarly, minimal residual diameter, percent residual stenosis, net gain, densitometric net area gain, and maximum pressure (2.2±5mm vs 2.1±0.6mm, 18±17% vs 23±15%, 0.8±0.5mm vs 0.8±0.6mm, 48±25% vs 48±26%, 7.3±2atm. vs 6.8±3atm., respectively) values were not statistically different between compliant and non-compliant ballon groups.
Major in-hospital complications, dissections caused by the study balloon (mostly type A and B), crossover and bail-out procedures (5 vs 3, 34 vs 32, 4 vs 3, 13 vs 14, respectively) were similar for both compliant and non-compliant balloon groups. Study balloon success rate (defined as <50% residuel stenosis or >20% net gain in the absence of major in-hospital complications, crossovers and bail-outs) and overall procedural success rate (80% vs 74%, 90% vs 85%) were not statistically different for compliant and non-compliant balloons.
In conclusion, we did not observe any statistically significant difference between compliant and non-compliant balloons in terms of immediate procedural results.

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It has been proposed that directional coronary atherectomy (DCA) should be an intervention of choice in larger vessels as one can achieve a greater minimal luminal diameter with DCA than with percutaneous transluminal coronary angioplasty (PTCA). This in turn should translate into a higher success rate and may even reduce the restenosis rate. The aim of this study was to compare DCA versus PTCA in vessels >3mm in diameter. One hundred fifty consecutive patients who met the inclusion criteria and had DCA were compared to 150 similarly selected PTCA patients. PTCA patients were selected from the era immediately preceding the advent of DCA so that selection bias could be excluded. All patients with ostial lesions, restenosis, vessels <3mm in diameter, and vessels with more than two significant lesions were excluded. Distal segments and circumflex cases were excluded as they formed a small subsegment. Both groups were similar in terms of demographic, clinical and angiographic variables. Quantitative analysis showed that the initial net gain was significantly greater in the DCA group than in the PTCA group (2.36±0.8mm vs. 1.78±0.7mm; p<0.05). Residual stenosis was 11% with DCA compared to 33% with PTCA (p<0.05). Despite these improved anatomical results the procedural success rates were similar (91.5% vs 84%). Major in hospital complications (death, acute occlusion, MI, emergency CABG, re-do) were higher in the DCA group than in the PTCA group (12% vs 6%). Clinical follow-up on 276 patients (150 DCA vs 126 PTCA) showed a 6 month clinical restenosis rate of 18% vs 28%, respectively. The incidence of re-do in 24 hours for acute occlusion was 6% for DCA and 1% for PTCA. In large-sized vessels DCA results in a lower restenosis rate. However, despite a lower incidence of residual stenosis, the complication rate tends to be higher with DCA (p<0.05).

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The long-term outcome in 198 patients with triple-vessel disease (TVD) treated medically was investigated. The patients, who underwent coronary angiography between September 1973 and February 1984, had significant (75% or more) stenotic lesions in all three major coronary arteries. The mean follow-up period was 8.4 years. The 5- and 10-year survival rates were 80.7% and 64.2%, respectively. Cardiac death occurred in 73 patients (36.9%) and nonfatal cardiac events developed in 60 patients (30.9%) during follow-up. When cardiac death and nonfatal myocardial infarction (MI) were defined as cardiac events, the annual attrition rate was 4.7%. There was no difference in survival with regard to the presence or absence of MI, the site of infarction, or the presence of total occlusion. In the AP group, however, the survival rate decreased as the number of totally-occluded arteries increased. In the MI group, the survival rate was not altered by the number of totally-occluded arteries, but was affected by the ejection fraction (EF). The 5-year survival rate was better in patients with good left ventricular function (EF≥60%) than in those with impaired left ventricular function (EF<60%), although the 10-year survival rate was similarly low in both groups. Revascularization such as PTCA or CABG might improve the long-term outcome in patients with TVD.

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Racemic sotalol has demonstrated anti-arrhythmic properties which include Class II (β blockade) and Class III (potassium channel blockade) activity. The Class II activity is demonstrated primarily in l-sotalol, and Class III activity is almost equipotent in each isomer.
Class II and Class III activity of dl-sotalol was investigated following repeated oral administration (80mg b. i. d.) for 7 days. Class II activity was evaluated according to the low frequency spectral power obtained by fast Fourier analysis of the R-R interval variation. Class III activity was evaluated according to the change in the QTc interval of the surface electrocardiogram.
The low frequency spectral power decreased after administration of the first dose on day 1 and this trend continued throughout the duration of the study. The QTc interval did not change with dl-sotalol administration.
These findings may suggest that Class II activity is more potent than Class III activity.

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Chronic mechanical stress of the heart secondary to arterial hypertension is a primary cause of left ventricular hypertrophy (LVH). The renin-angiotensin system (RAS) plays an important role in the cardiovascular system, regulating the expression of cardiac hypertrophy, in part, independent of the effects of systemic hypertension. A major component of RAS is angiotensin converting enzyme (ACE), which is upregulated in pressure overload-induced cardiac hypertrophy as well as heart failure. In a recent study, we found that the T allele of the M235T polymorphism of the angiotensinogen gene in sporadic hypertrophic cardiomyopathy (HCM) patients is associated with LVH. The present study was designed to assess the contribution of the polymorphisms of the angiotensin II type 1 receptor (AGT₁R A¹¹⁶⁶C) genes on development of left ventricular hypertrophy. Patients with hypertensive LVH and relatives of HCM without manifesting the disease, showed higher C allele frequency compared to patients with HCM (11.3% vs 4.2%, χ²=5.3, p<0.05 and 10.5% vs 4.2%, χ²=5.3, p<0.05, respectively), but healthy controls did not (11.3% vs 7.5%, χ²=1.42, NS and 10.5% vs 7.5%, χ²=1.2, NS).
The strong interaction between ACE I/D and AGT₁R A¹¹⁶⁶C gene polymorphisms has been found in groups of relatives of HCM patients; odds ratio associated with ACE D allele was significant in subjects carrying the AGT₁R C allele (OR=7.3, 95% CI 1.6-33.1; χ²=7.9, p<0.02) compared with healthy subjects.
We conclude that the molecular variant of the AGT₁R A¹¹⁶⁶C gene is not contributing to the development of cardiac hypertrophy in hypertensive LVH and HCM patients, whereas carriers of both C and D alleles had a four-fold increase in the odds ratio for family history of HCM without manifesting the disease.

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The aim of the present study was to clarify myocardial collagen metabolism in cardiomyopathic hamsters and the effects of the angiotensin converting enzyme inhibitor, captopril, on collagen synthesis.
Cardiac fibroblasts from Bio 14.6 cardiomyopathic hamsters and from non-cardiomyopathic F1b hamsters were cultured and used in the 4th passage. The synthetic activity of collagenous protein from the two types of hamsters was determined by measuring ³H-proline uptake, and the collagen type was subsequently analyzed by SDS-PAGE in cultured cardiac fibroblasts. Also studied were the effects of the angiotensin converting enzyme inhibitor captopril (1μM) on collagen synthesis by cardiac fibroblasts from cardiomyopathic hamsters.
Twenty five-week-old Bio 14.6 hamsters had significantly higher synthetic activity of collagenous protein and rate of collagen synthesis compared with 13-week-old Bio 14.6 hamsters or 25-week-old F1b hamsters [Bio 14.6 (25-week); 12.4±1.6, Bio 14.6 (13-week); 4.8±0.4, F1b (25-week); 8.7±0.9cpm/cell, Bio 14.6 (25-week); 11.0±0.9, Bio 14.6 (13-week); 3.9±0.4, F1b (25-week); 4.8±0.4%, p<0.05]. Qualitatively, 25-week-old Bio 14.6 hamsters had significandy higher synthetic activity of type I, III, IV and V collagens compared with 25-week-old F1b hamsters. The synthetic activity of type III collagen was incrcased the most in the cardiomyopathic group. Captopril (1μM) causcd a significant decrease in synthetic activity of collagenous protein in 25-week-old Bio 14.6 hamsters (12.4±1.6cpm/cell→10.9±1.1cpm/cell, p<0.05). Qualitatively, the synthetic activity of type III collagen was decreased to about half.
Our study revealed enhanced collagen synthetic activity in cardiac fibroblasts from Bio 14.6 hamsters. Captopril improved collagen metabolism in cultured cardiac fibroblasts from Bio 14.6 hamsters not only quantitatively but also qualitatively. The mechanism of this improvement may be related to the cardiac renin angiotensin system.

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This study compared renal and intestinal handling of sodium in Dahl-Iwai salt-sensitive (S) and salt-resistant (R) rats given a normal-salt diet (0.3%NaCl) and a high-salt diet (4.0%NaCl). Six-week-old female S and R rats (n=7 each) were given a normal-salt diet for 14 days followed by a high-salt diet for 3 weeks. Systolic blood pressure was significantly higher in the S rats than in the R rats only at the end of the high-salt diet period (170±5, mean±SEM, vs 152±1mmHg, p<0.01). Daily sodium intake, water intake, urine volume, and urinary and fecal excretions did not significantly differ between the R and the S rats during the normal- and high-salt diets, except for a slight, although significant, decrease in fecal sodium excretion in the S rats as compared with the R rats in the 2nd week of the high-salt diet period. After switching from the normal-salt diet to the high-salt diet, urinary sodium excretion increased by 17- to 18-fold and fecal sodium excretion increased by about 5-fold in the 1st week of salt loading. The changes in urinary and fecal sodium excretions did not differ significantly betweeen the groups. Cumulative sodium retention was similar in the two groups. The aldosterone/creatinine ratio in 24-hr urine, which was significantly lower in the S than in the R rats during the normal-salt diet, decreased to similar levels in both groups after salt loading, indicating a blunted response of aldosterone in the S rats. Thus, there were no discernible differences in renal and intestinal handling of sodium between the S and the R rats, except for a slight, but significant, difference in fecal sodium excretion in the 2nd week of the high-salt period. The results indicate that inappropriate suppression of aldosterone or some other mechanism induced by salt loading may be involved in blood pressure elevation in Dahl-Iwai S rats.

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