No abstract

A total of 239 patients undergoing serial coronary angiography with a concomitant ergonovine provocation test were studied between July 1974 and June 1987. The progression of coronary artery disease was evaluated in relation to risk factors, especially coronary artery spasm. Patients were classified into three groups: 1) new myocardial infarction group (39 patients); 2) progression without infarction group (90 patients); and 3) nonprogression group (110 patients). To assess how risk factors and coronary spasm are related to the occurrence of new myocardial infarction and progression without infarction, 11 variables in the three groups were examined: age, gender, the time interval between the studies, fasting blood sugar, systolic blood pressure, diastolic blood pressure, smoking, serum cholesterol, triglyceride, uric acid and a positive response to the ergonovine provocation test. Multiple regression analysis selected three independent predictors of progression without infarction: cholesterol (p less than 0.01), systolic blood pressure (p less than 0.05) and a positive response to the ergonovine provocation test (p less than 0.001). Multiple regression analysis also selected three independent predictors of the occurrence of new myocardial infarction: fasting blood sugar (p less than 0.01), systolic blood pressure (p less than 0.05) and a positive response to the ergonovine provocation test (p less than 0.001). A positive response to the ergonovine provocation test was the strongest factor for occurrence of both new myocardial infarction and progression without infarction. To evaluate segmental arterial changes, 3,275 coronary artery segments were analyzed in the 239 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous transvenous mitral commissurotomy was performed in 106 consecutive patients. Significant symptomatic improvement was achieved in 97 patients (92%). Mean left atrial pressure decreased (from 18 +/- 8 to 11 +/- 8 mm Hg, p less than 0.00001), mean mitral diastolic pressure gradient decreased (from 12 +/- 7 to 7 +/- 6 mm Hg, p less than 0.00001), and mitral valve area increased (from 1.40 +/- 0.40 to 2.00 +/- 0.50 cm2, p less than 0.00001). Based on echocardiographic characteristics of the mitral apparatus, patients were grouped retrospectively in three categories: pliable (group 1, n = 37), semipliable (group 2, n = 59), and rigid (group 3, n = 10). Clinical success was achieved in 36 patients of group 1 (97%) and in 55 patients of group 2 (93%). Only six patients in group 3 (60%) improved symptomatically (p less than 0.001 vs. group 1, p less than 0.001 vs. group 2). The severity of mitral regurgitation increased in five patients of group 1 (14%), in 12 of group 2 (20%), and in three of group 3 (33%). Six patients had recurrent symptoms at 9 months after commissurotomy. Recurrence of symptoms was significantly more frequent in group 3 compared with the other two groups (group 1, 3%; group 2, 4%; and group 3, 50%; p less than 0.0001 vs. groups 1 and 2). Multiple regression analysis identified the previously mentioned echocardiographic characteristics of the mitral apparatus as the significant predictor for clinical outcome. Thus, percutaneous transvenous mitral commissurotomy can be considered a safe and effective treatment for patients with pliable valves. Patients with semipliable or with rigid valves should be selected for operation very carefully.

1 The classical ATP sensitive K + (K ATP ) channels are composed of a sulphonylurea receptor (SUR) and an inward rectifying K + channel subunit (BIR/Kir6.2). They are the targets of vasorelaxant agents called K + channel openers, such as pinacidil and nicorandil. 2 In order to examine the tissue selectivity of pinacidil and nicorandil, in vitro, we compared the e ects of these agents on cardiac type (SUR2A/Kir6.2) and vascular smooth muscle type (SUR2B/Kir6.2) of the K ATP channels heterologously expressed in HEK293T cells, a human embryonic kidney cell line, by using the patch-clamp method. 3 In the cell-attached recordings (145 mM K + in the pipette), pinacidil and nicorandil activated a weakly inwardly-rectifying, glibenclamide-sensitive 80 pS K + channel in both the transfected cells. 4 In the whole-cell con®guration, pinacidil showed a similar potency in activating the SUR 2B /Kir6.2 and SUR 2A /Kir6.2 channels (EC 50 of *2 and *10 mM, respectively). On the other hand, nicorandil activated the SUR 2B /Kir6.2 channel 4100 times more potently than the SUR 2A /Kir6.2 (EC 50 of *10 mM and 4500 mM, respectively). 5 Thus, nicorandil, but not pinacidil, preferentially activates the K ATP channels containing SUR 2B . Because SUR 2A and SUR 2B are diverse only in 42 amino acids at their C-terminal ends, it is strongly suggested that this short part of SUR 2B may play a critical role in the action of nicorandil on the vascular type classical K ATP channel.

The effects of potassium channel opening drugs and intracellular nucleotides on the ATP-sensitive K+ (KATP) channel composed of SUR2A and Kir6.2 in HEK293T cells were examined using the patch-clamp technique. The SUR2A/Kir6.2 channel was activated effectively by pinacidil, marginally by nicorandil but not by diazoxide. The pinacidil-activated channel currents were inhibited by glibenclamide with a Ki value of 160 nM. Upon formation of inside-out (I-O) patches, spontaneous openings of the channels appeared, which were inhibited by intracellular ATP (ATPi) equipotently in the presence and in the absence of intracellular Mg2+ (Mg2+i). The channel activity ran-down gradually in I-O patches. The run-down channels could be reactivated by ATPi only in the presence of Mg2+i. Uridine 5'-diphosphate (UDP) antagonized the ATPi-mediated inhibition of the channel activity before run-down. After run-down, UDP activated the channel without antagonizing ATPi-mediated channel inhibition. Thus, the SUR2A/Kir6.2 reproduced the major properties of the native cardiac KATP channel well in terms of nucleotide regulation and pharmacology, and therefore can be a useful tool with which to elucidate the molecular mechanisms characterizing the KATP channel.