L.Richard Smith

New formulas for the calculation of effective renal plasma flow

Estimation of effective renal plasma flow (ERPF) can be made easily, inexpensively, and accurately by means of a single plasma concentration determination, sampled 44 min after injection of 131I-orthoiodohippurate (OIH). We originally established predictive regression equations based on a series of patients with a wide variety of diseases and a few normal potential kidney donors. The equation best fitting that data was parabolic in form and assumed a negative slope when high ERPF rates were encountered. This problem has been corrected by deriving new equations (parabolic and exponential) based on an expanded series which includes a large number of subjects with high ERPF. Errors of estimation are lower than those of the more classic para-aminohippuric acid (PAH) clearances and well within the exigencies of clinical practice.

Enhancement of left ventricular function by glucose-insulin-potassium infusion in acute myocardial infarction

Abstract Twenty-eight patients admitted to the hospital with suspected acute myocardial infarction underwent baseline studies within 12 hours of onset of symptoms. Patients were then randomized to receive control infusion (0.45 percent sodium chloride at 20 ml/hour) (15 patients) or glucoseinsulin-potassium infusion (300 g glucose, 50 units regular insulin, 80 mEq KCl/liter water at 1.5 ml/kg per hour) (13 patients) for 48 hours. All patients received 0.45 percent sodium chloride for 2 more days. Coronary arteriograms and left ventriculograms were obtained in 26 (93 percent) of 28 patients 2 to 3 weeks after infarction. Radionuclide ejection fraction improved during glucose-insulin-potassium infusion (49 ± 4 to 55 ± 5 percent, p During experimental infusion pulmonary arterial end-diastolic pressure decreased in the glucose-insulin-potassium group (17 ± 2 to 12 ± 2 mm Hg, p These data suggest that glucose-insulin-potassium infusion after acute myocardial infarction in human beings (1) increases global ejection fraction, (2) Increases ejection fraction in the “infarcted zone” without changing ejection fraction in the “noninfarcted zone”, and (3) decreases pulmonary arterial end-diastolic pressure and end-diastolic and end-systolic volumes.

Clinical effects of glucose-insulin-potassium on left ventricular function in acute myocardial infarction: Results from a randomized clinical trial

Abstract The effects of glucose-insulin-potassium (GIK) on hemodynamics and left ventricular (LV) function in patients with acute myocardial infarction (AMI) were investigated in a prospective randomized study. Patients who presented with suspected AMI were candidates for this study if prerandomization evaluation was completed within 12 hours from onset of chest pain. Patients over 75 years of age, insulin-dependent diabetics, patients with renal insufficlency, and comatose patients were excluded. Following completion of baseline hemodynamic measurements, patients were randomly allocated to 48-hour infusion of 300 gm G, 500 units I, and 80 mEq KCl per liter at rate of 1.5 ml/kg/hr or to conventional therapy. In addition to serial hemodynamic measurements, dextran LV function curves (LVFC) were constructed during the second and third days to assess extent of LV injury. Eighty-five of 118 patients who were initially randomized into this study had AMI documented by diagnostic rise and fall of CK-MB isoenzyme. Baseline characteristics and hemodynamics were similar for GIK and control patients with AMI. GIK patients who presented with their initial AMI had significant reduction in pulmonary arterial end-diastolic pressure from prerandomization value of 16 ± 1 to 10 ± 1 by day 3, compared to 18 ± 1 to 16 ± 1 mm Hg for control patients ( p 2 for control patients ( p p p

Lofexidine and clonidine in moderate essential hypertension

The efficacy, safety, and tolerability of lofexidine, a centrally acting imidazoline derivative, were compared to that of clonidine in a randomized double‐blind trial in 28 patients with moderate essential hypertension. The study consisted of a washout phase, a placebo phase, a drug titration phase (0.2 to 1.6 mglday, with hydrochlorothiazide added at 0.4 mg daily for supine and erect diastolic blood pressure above 90 mm Hg), and a maintenance phase lasting 3 mo. During the titration phase supine systolic and diastolic pressures fell in lofexidine patients from 143 ± 4198 ± 3 to 122 ± 3181 ± 2 mm Hg and in clonidine patients from 154 ± 61101 ± 2 to 124 ± 4/81 ± 2 mm Hg (P < 0.01), and erect systolic and diastolic pressures fell in lofexidine patients from 143 ± 31105 ±2 to 116 ± 3185 ± 2 mm Hg and in clonidine patients from 156 ± 6/104 + 2 to 117 ± 4/82 ± 2 mm Hg (P < 0.01). Maximal doses of lofexidine and clonidine in combination with hydrochlorothiazide had equivalent antihypertensive effects, but when the effects of lofexidine and clonidine were compared at each dose level, larger doses of lofexidine were needed to control blood pressure. There was no change in heart rate in lofexidine patients in either the supine or erect position during the titration phase but heart rate fell in the clonidine patients (P < 0.05) over the same period. Dry mouth and drowsiness were reported in both groups but were both less frequent and less severe in the lofexidine group than the clonidine group.

Heparin and Infarct Coronary Artery Patency After Streptokinase in Acute Myocardial Infarction

Anticoagulant therapy is frequently used after thrombolytic agents in the treatment of acute myocardial infarction (AMI) although it is unclear that such therapy will prevent subsequent infarct vessel reocclusion. The role of duration of heparin therapy in maintaining infarct artery patency was studied retrospectively in 53 consecutive AMI patients who received streptokinase therapy and underwent coronary angiography acutely and at 14 +/- 1 days. Of the 39 patients with initial infarct vessel patency, patency at follow-up angiography was observed in 100% (22 of 22) of those who received greater than or equal to 4 days of intravenous heparin but in only 59% (10 of 17) of those patients who received less than 4 days of heparin (p less than 0.05). Of the 14 patients not initially recanalized after streptokinase, patent infarct-related arteries at follow-up angiography were found in 3 of 8 (38%) treated with greater than or equal to 4 days of heparin therapy but in none of the 6 patients treated for less than 4 days (difference not significant). No significant difference in hemorrhagic complications was noted between the short- and long-term heparin treatment groups. Thus, greater than or equal to 4 days of intravenous heparin therapy after successful streptokinase therapy in AMI is more effective in maintaining short-term infarct vessel patency than a shorter duration of therapy and it may maintain the short-term patency of the infarct vessel in those patients who later spontaneously recanalize.

Prediction of urinary excretion of 131I-orthoiodohippurate

A new formula is presented for the prediction of urinary excretion at approximately 35 min after injection of 131I-orthoiodohippurate, derived from a large series of normal kidney donors, before and after unilateral nephrectomy, and a few patients with diseases in which there was no evidence of urinary tract obstruction. The best formula was: Expected percent dose excretion at 35 min = 79.3[1−e−(0.004798 x ERPF)] with a standard error of estimate (Sy·x) of 5.2% dose. This value has been particularly useful in clinical practice in the calculation of an excretion index (actual/expected percent dose excretion) which separates various post-transplantation entities and various nephrouologic processes.

Effect of morphine on the heart rate response to noxious stimulation: Interaction with halothane and naloxone

Abstract The effect of morphine on the heart rate increase, in response to noxious somatic stimulation, was studied in 125 rat experiments. It was found that halothane, in a subanesthetic concentration of 0.3 vol%, profoundly weakened the effect of morphine on the heart rate response. As a result, the morphine ED50 value for blockade of the heart rate response was increased from 5.9 to 46.1 mg/kg (P < 0.001). Naloxone in a dose of 0.05 mg/kg increased the morphine ED50 value for blockade of the heart rate response 11‐fold (morphine was administered without halothane). However, the same dose of naloxone did not change the morphine ED50 value obtained with combined administration of morphine and halothane. An increase in the naloxone dosage (up to 1 mg/kg) was necessary to demonstrate the naloxone antagonistic effect (8‐fold increase in the morphine ED50 value) when morphine was given with halothane. It has been suggested that the effect of morphine on the heart rate response to noxious stimulation results primarily from the activation of inhibitory control mechanisms concerned with this response (indirect effect). Halothane depresses the inhibitory control mechanisms and, therefore, weakens the effect of morphine. A significant increase in doses of morphine is needed to provide the direct antinociceptive effect.

Computer Acquisition and Processing of Left Ventricular Echocardiograms

An echocardiographic digital image processing system has been constructed to quantify left ventricular (LV) dynamics. The system utilizes a commercial 8 bit analog-to-digital convertor (ADC) that encodes A-scan information from the echo pulses. The high rate conversions are stored in a shift register buffer memory, and between echo pulses are transmitted at reduced rate to the computer. A scan convertor with 32 levels of grey scale is used to display raw and processed echo data, physiological signals and alphanumerics at a remote computer terminal.