Sakti Mookherjee

Effects of tiodazosin, a new antihypertensive, hemodynamics and clinical variables

Tiodazosin, a new antihypertensive, resembles prazosin in structure and α‐adrenergic‐blocking activity, and it also exerts a direct vasodilator effect. We evaluated its long‐term hemodynamic and systemic effects in patients with essential hypertension. Our data show that after 10 wk of therapy with tiodazosin, 7 of our 10 patients had significant reduction in intra‐arterial mean blood pressure as a result of a fall in systemic vascular resistance. Heart rate, cardiac output, and plasma volume did not change. Systemic effects were minor and included a gain in weight and a reduction in hemoglobin, hematocrit, platelet count, serum protein, albumin, bilirubin, and specific gravity of urine. No patient initially developed orthostatic symptoms after the first dose, but there were transient episodes of light‐headedness in three patients, palpitations in two, increased urinary frequency in one, and drooping of eyelid in another during the trial period. One patient developed profound orthostatic hypotension, which could be attributed to the drug. Because of such side effects and the failure to lower blood pressure in 30% of patients with essential hypertension, tiodazosin appears to have several important drawbacks and little advantage over currently available antihypertensives.

Atrial natriuretic peptide response to cardioversion of atrial flutter and fibrillation and role of associated heart failure.

Plasma atrial natriuretic peptide (ANP) concentrations were measured before and 1 hour after cardioversion in 40 patients (27 with atrial flutter and 13 with atrial fibrillation) admitted for elective cardioversion. Fourteen (11 with atrial flutter and 3 with atrial fibrillation) had clinical evidence of congestive heart failure (CHF). Conversion to sinus rhythm was successful in 39 patients. The mean ANP concentration in the entire group decreased after cardioversion from 38 +/- 4 to 17 +/- 2 pmol/liter (p less than 0.001). In the subgroup with CHF, the ANP level, which was not significantly higher than that in the group without CHF, decreased from 47 +/- 8 to 19 +/- 3 pmol/liter (p less than 0.01). Neither mode of cardioversion (spontaneous 1, pharmacologic 2 and direct-current countershock 36) nor associated CHF influenced ANP response to cardioversion. One patient with atrial flutter and failed cardioversion had unchanged ANP level. The decrease after cardioversion in ANP concentration correlated with its control level (r = 0.88, p less than 0.001) but not with the decrease in heart rate. The ANP level in patients with atrial fibrillation was 45 +/- 9 vs 38 +/- 5 pmol/liter in those with atrial flutter (difference not significant). Arrhythmia duration, left atrial size, and ventricular rate or arterial blood pressure did not correlate with ANP concentration in any subgroup. It is concluded that (1) the ANP level is elevated comparably in patients with both atrial flutter and fibrillation regardless of the presence or absence of CHF; and (2) the level decreases, independent of the mode of cardioversion or presence of CHF, promptly after successful cardioversion.

Electrocardiographic criteria for the diagnosis of combined inferior myocardial infarction and left anterior hemiblock

New electrocardiographic (ECG) criteria for diagnosing the combination of inferior myocardial infarction and left anterior hemiblock are proposed. The proposed criteria are based upon the relations between portions of the vectorcardiographic QRS loop in the frontal plane and the corresponding portions of the QRS complexes recorded by the limb leads. The application of the proposed criteria requires that the tracings be obtained with 3-channel ECG machines. The proposed criteria for the diagnosis of inferior myocardial infarction and left anterior hemiblock are as follows: (1) leads aVR and aVL both end in R waves, with the peak of the terminal R wave in lead aVR occurring later than the peak of the terminal R wave in lead aVL, and (2) a Q wave of any magnitude is present in lead II. The performance of the proposed criteria was superior to that of 10 combinations of traditional ECG criteria for inferior myocardial infarction and left anterior hemiblock.

Electrocardiographs criteria for the diagnosis of anterior myocardial infarction: Importance of the duration of precordial R waves

A systematic evaluation of a large number of electrocardiographic (ECG) variables that might be useful for diagnosing anterior myocardial infarction (MI) is reported. Previous anterior MI was shown to be present or absent by cardiac catheterization in 199 patients. The best discriminator between cases and noncases of anterior MI in most patients is the presence of a Q wave of any magnitude or an initial R wave less than 20 ms in lead V2. In patients with ECG evidence of associated left ventricular or type C right ventricular enlargement, the more stringent criterion of a Q wave of any magnitude in lead V2 yielded the optimal combination of sensitivity and specificity for diagnosing anterior MI. The diagnostic performance of the proposed criteria for anterior MI is superior to that of more traditional criteria that use measurements of the absolute and relative amplitudes of precordial R waves.

Improved electrocardiographic criteria for the diagnosis of left anterior hemiblock

New electrocardiographic (ECG) criteria for the diagnosis of left anterior hemiblock are proposed. The proposed criteria are based upon the relation between portions of the vectorcardiographic (VCG) QRS loop in the frontal plane and the corresponding portions of the ECG QRS complexes recorded by the limb leads. The application of the proposed criteria requires that the tracings be obtained with 3-channel ECG machines so that the temporal relation between the QRS complexes in simultaneously recorded limb leads can be inspected. This type of analysis of the electrocardiogram permits prediction of features of the VCG QRS loop that are important for the diagnosis of left anterior hemiblock. The proposed ECG criteria for the diagnosis of left anterior hemiblock are (1) the QRS complexes in leads aVR and aVL each end in an R wave (terminal R wave), and (2) the peak of the terminal R wave in lead aVR occurs later than the peak of the terminal R wave in lead aVL. The sensitivity and specificity of the proposed criteria were empirically evaluated using series of electrocardiograms obtained under clinical circumstances during which the occurrence of left anterior hemiblock was, respectively, likely and unlikely. The performance of the proposed criteria was statistically superior to that of 2 sets of frontal plane QRS axis criteria.

Comparison of optimal scalar electrocardiographic, orthogonal electrocardiographic and vectorcardiographic criteria for diagnosing inferior and anterior myocardial infarction

A scalar electrocardiogram (ECG), orthogonal ECG and vectorcardiogram (VCG) were recorded in 46 normal persons, 38 patients with inferior myocardial infarction (MI) and 22 patients with anterior MI proved at cardiac catheterization. The diagnostic information provided by the scalar ECG, orthogonal ECG and VCG was quantitatively analyzed and the optimal criteria for diagnosing inferior and anterior MI exhibited by each method were identified. The optimal scalar electrocardiographic, orthogonal electrocardiographic and vectorcardiographic criteria, respectively, are: For inferior MI: initial superior duration in lead aVF greater than 30 ms (sensitivity 63%, specificity 100%), superior/inferior amplitude ratio in lead Y greater than or equal to 0.2 (sensitivity 63%, specificity 96%), initial superior duration greater than 29 ms or initial superior distance greater than 0.4 mV in the frontal plane loop (sensitivity 68%, specificity 100%). For anterior MI: initial anterior duration in lead V2 less than 20 ms or initial anterior duration in lead V3 less than 25 ms (sensitivity 91%, specificity 100%), anterior/posterior duration ratio in lead Z less than 0.3 (sensitivity 73%, specificity 98%), initial anterior duration less than 15 ms in the transverse plane loop (sensitivity 64%, specificity 98%). There were no significant differences among the performances of the optimal scalar ECG, orthogonal ECG and the VCG for diagnosing inferior MI. However, the performance of the optimal scalar ECG was superior to that of the optimal orthogonal ECG and the optimal VCG for diagnosing anterior MI (chi-square = 5.20, p less than 0.02 and chi-square = 7.14, p greater than 0.01, respectively).

Diagnostic significance for coronary artery disease of abnormal Q waves in the “lateral” electrocardiographic leads

To determine the diagnostic significance for coronary artery disease of abnormally large Q waves in leads I, aVL, V5 and V6--the lateral electrocardiographic leads--the electrocardiograms of 240 patients who had undergone cardiac catheterization were studied. First, the electrocardiograms of 99 subjects proved normal by cardiac catheterization (group 1) were studied to determine the values of the durations of Q waves in leads I, aVL, V5 and V6 that should be exceeded to be considered abnormal. These values were 30, 30, 20 and 25 ms, respectively. Then, 67 patients were identified who had abnormal Q waves in at least 1 of these leads (group 2) and 74 patients with at least 1 angiographic abnormality but without abnormal Q waves in any of these leads (group 3). Group 2 had generally more extensive left ventricular disease and a higher prevalence of anterior, inferior and apical healed myocardial infarction (MI) than group 3. However, compared with group 3, group 2 had lower prevalences of significant narrowing of the coronary arteries that supply the left ventricular lateral wall. Within group 2, abnormal Q waves in leads I and aVL (traditionally designated high lateral MI) were associated with anterior as well as apical MI, and abnormal Q waves in leads V5 and V6 (traditionally designated anterolateral MI) were associated with inferior as well as apical MI. Thus, abnormal Q waves in leads I, aVL, V5 and V6 tend to reflect apical rather than lateral MI and the term anterolateral MI is especially misleading.

Lack of relationship between plasma insulin and glucagon levels and angiographically-documented coronary atherosclerosis☆

In 120 consecutive patients undergoing diagnostic coronary arteriography, fasting blood glucose, plasma insulin, glucagon, serum cholesterol and triglyceride concentrations were measured. The insulin-glucose ratio and insulin-glucagon ratio were calculated. Forty-five patients had normal coronary arteries, 19 had single vessel coronary artery disease and 56 patients had multiple vessel disease. Fasting blood glucose was greater than 120 mg/100 ml in 37 patients (group A) and included 9 of the 10 known diabetics, 3 of whom were being treated with insulin. Seventy-seven patients included in group B had fasting blood glucose concentration less than 120 mg/100 ml. Patients with multiple vessel coronary disease in either group had higher blood glucose and cholesterol concentrations than those with normal coronary arteries or the ones with single vessel disease, but they did not have higher plasma insulin or glucagon levels nor increased insulin-glucose or insulin-glucagon ratios. With comparable extent of coronary artery disease patients in group A had higher plasma insulin levels and insulin-glucagon ratios than those in group B, but no correlation exists between the presence or extent of coronary atherosclerosis and these variables in either group. Thus, neither fasting plasma insulin level nor insulin-glucagon ratio predicts the status of underlying coronary atherosclerosis in either diabetics or nondiabetics.

Systemic and pulmonary hemodynamic effects of saralasin infusion in hypertension: Predictability of plasma renin status from hemodynamic changes☆

Hemodynamic measurements were obtained before and after 30 minutes of saralasin infusion in 26 fasting adults with hypertension (25 men and 1 woman). Nine showed a depressor response with a decrease in mean intaarterial pressure greater than 20 mm Hg. Ten were nonresponders and seven had an agonistic response with an increase in mean arterial pressure of greater than 10 mm Hg. Heart rate, pulmonary arterial and wedge pressures and pulmonary vascular resistance were nearly identical in the three groups and remained unchanged. Cardiac index decreased from a mean of 2.76 +/- 0.14 (standard error of the mean) to 2.48 +/- 0.1 liters/min per m2 in the nonresponders (P less than 0.02) but remained unchanged in the groups with a depressor or an agonistic response. The mean systemic vascular resistance decreased from 2,406 +/- 303 to 1,839 +/- 265 dynes sec/cm5 in the group with a depressor response (P less than 0.001) and increased in nonresponders (less than 0.02) and those with an agonistic response (P less than 0.01). However, regardless of the response of mean arterial pressure, systemic vascular resistance decreased only in the 10 patients with a plasma renin activity greater than 5 ng/ml per hour (8 from the depressor response group and 1 each from the nonresponse and agonistic response groups). It is concluded that (1) classification based soley on the response of aterial pressure to saralasin ignores important hemodynamic changes; (2) the response of cardiac index--no change in the patients with a depressor response and a reduction in nonresponders--suggests that endogenous angiotension II supports cardiac output in these groups; (3) a decrease in systemic vascular resistance is better than a decrease in mean arteiral pressure as a predictor of the status of the plasma renin activity; and (4) lack of change in pulmonary vascular resistance suggests that endogenous angiotension II plays an insignificant role in maintaining the resistance of the pulmonary vasculature.

Importance of the terminal portion of the QRS in the electrocardiographic diagnosis of inferior myocardial infarction

The scalar electrocardiograms of 64 patients with inferior wall myocardial infarction (MI) and 87 normal subjects were quantitatively analyzed to determine the respective contributions of the initial and terminal portions of the QRS to the diagnosis of inferior MI. Of the 10 best individual electrocardiographic criteria for inferior MI, 7 were Q-wave criteria and 3 were criteria that consisted of delayed termination of the QRS in leads II or III. Combining the best terminal QRS criterion (the QRS in lead III ending at least 20 ms later than the QRS in lead I) with the 7 best Q-wave criteria and the best Q-wave criterion (Q wave 40 ms or longer in lead aVF) with the 3 best terminal QRS criteria, resulted in criteria with better sensitivities and overall diagnostic performances than those of the individual criteria. Analyzing the vectorcardiograms that were also available in 26 of the patients with inferior MI and 34 of the normal subjects showed that the delayed inscription of the end of the QRS in leads II and III in patients with inferior MI is due to redirection of the terminal forces of ventricular depolarization. The terminal portions of the QRS complexes in the limb leads, considered both alone and in conjunction with traditional measurements of Q waves, contain information that is useful for diagnosing inferior MI.