The Pharmacological Basis of Therapeutics A Textbook of Pharmacology, Toxicology and Therapeutics for Physicians and Medical Students. By Prof. Louis Goodman and Prof. Alfred Gilman. Pp. xiii + 1383. (New York: The Macmillan Company, 1941.) 50s. net.

The Pharmacological Basis of Therapeutics

The postmortem findings and clinical records of 27 patients with proved diabetic glomerulosclerosis were examined and reviewed for evidence of primary myocardial disease. Twenty-three cases were excluded because of complicating conditions such as hypertension, significant obstruction of the major coronary arteries or valvular disease. Four patients demonstrated cardiomegaly and congestive heart failure of no known cause. The autopsy findings consisted of left ventricular hypertrophy and, in 1 case, right ventricular hypertrophy as well, in the absence of major coronary artery disease. Histopathologic study revealed diffuse fibrotic strands extending between bundles of muscle fibers and myofibrillar hypertrophy. In 1 case, the small intramural coronary arterioles demonstrated thickening of the wall and narrowing of the lumen due primarily to the deposition of acid mucopolysaccharide material in the subendothelial layers and subsequent subintimal thickening and medial hypertrophy. It is postulated that the myocardial disease seen in these cases is probably secondary to diabetic mjcroangiopathy although the direct effects of the abnormal myocardial metabolism in diabetes could not be excluded.

New type of cardiomyopathy associated with diabetic glomerulosclerosis

Swynghedauw, Bernard. Molecular Mechanisms of Myocardial Remodeling. Physiol. Rev. 79: 215–262, 1999. — “Remodeling” implies changes that result in rearrangement of normally existing structures. Th...

Molecular Mechanisms of Myocardial Remodeling

Institutional Affiliations Chair Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Task Force 1 Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Anderson A: University of Chicago, Chicago, Illinois, USA; Chan M: University of Alberta, Edmonton, Alberta, Canada; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA; Fedson S: University of Chicago, Chicago, Illinois, USA; Fisher P: Ochsner Clinic, New Orleans, Louisiana, USA; Gonzales-Stawinski G: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Martinelli L: Ospedale Niguarda, Milano, Italy; McGiffin D: University of Alabama, Birmingham, Alabama, USA; Parisi F: Ospedale Pediatrico Bambino Gesu, Rome, Italy; Smith J: Freeman Hospital, Newcastle upon Tyne, UK Task Force 2 Taylor D: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Meiser B: University of Munich/Grosshaden, Munich, Germany; Baran D: Newark Beth Israel Medical Center, Newark, New Jersey, USA; Carboni M: Duke University Medical Center, Durham, North Carolina, USA; Dengler T: University of Hidelberg, Heidelberg, Germany; Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, USA; Frigerio M: Ospedale Niguarda, Milano, Italy; Kfoury A: Intermountain Medical Center, Murray, Utah, USA; Kim D: University of Alberta, Edmonton, Alberta, Canada; Kobashigawa J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Shullo M: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Stehlik J: University of Utah, Salt Lake City, Utah, USA; Teuteberg J: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Uber P: University of Maryland, Baltimore, Maryland, USA; Zuckermann A: University of Vienna, Vienna, Austria. Task Force 3 Hunt S: Stanford University, Palo Alto, California, USA; Burch M: Great Ormond Street Hospital, London, UK; Bhat G: Advocate Christ Medical Center, Oak Lawn, Illinois, USA; Canter C: St. Louis Children Hospital, St. Louis, Missouri, USA; Chinnock R: Loma Linda University Children's Hospital, Loma Linda, California, USA; Crespo-Leiro M: Hospital Universitario A Coruna, La Coruna, Spain; Delgado R: Texas Heart Institute, Houston, Texas, USA; Dobbels F: Katholieke Universiteit Leuven, Leuven, Belgium; Grady K: Northwestern University, Chicago, Illlinois, USA; Kao W: University of Wisconsin, Madison Wisconsin, USA; Lamour J: Montefiore Medical Center, New York, New York, USA; Parry G: Freeman Hospital, Newcastle upon Tyne, UK; Patel J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Pini D: Istituto Clinico Humanitas, Rozzano, Italy; Pinney S: Mount Sinai Medical Center, New York, New York, USA; Towbin J: Cincinnati Children's Hospital, Cincinnati, Ohio, USA; Wolfel G: University of Colorado, Denver, Colorado, USA Independent Reviewers Delgado D: University of Toronto, Toronto, Ontario, Canada; Eisen H: Drexler University College of Medicine, Philadelphia, Pennsylvania, USA; Goldberg L: University of Pennsylvania, Philadelphia, Pennsylvania, USA; Hosenpud J: Mayo Clinic, Jacksonville, Florida, USA; Johnson M: University of Wisconsin, Madison, Wisconsin, USA; Keogh A: St Vincent Hospital, Sidney, New South Wales, Australia; Lewis C: Papworth Hospital Cambridge, UK; O'Connell J: St. Joseph Hospital, Atlanta, Georgia, USA; Rogers J: Duke University Medical Center, Durham, North Carolina, USA; Ross H: University of Toronto, Toronto, Ontario, Canada; Russell S: Johns Hopkins Hospital, Baltimore, Maryland, USA; Vanhaecke J: University Hospital Gasthuisberg, Leuven, Belgium.

http://www.jsht.jp/uploads/ISHLT_GL_TaskForce2_110810.pdf

The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients

A technique was developed for measurement of blood flow in the coronary sinus in man by continuous thermodilution. For single determinations, 5% dextrose at room temperature is injected at a constant rate of 35 ml/min for a period of about 20 sec. In 14 subjects with normal coronary arteries the mean coronary sinus blood flow was 122 ± 25 ml/min (range, 83 to 159 ml/min). The blood flow computed per 100 g of left ventricle was 82 ± 16 ml/min, which is in the range of values obtained by nitrous oxide and coincidence counting methods. In 35 patients with arteriographically confirmed coronary artery disease the mean flow was similar (128 ± 20 ml/min; range, 92 to 167 ml/min). A special catheter was used for simultaneous measurement of blood flow in the coronary sinus and great cardiac vein. In eight normal subjects the mean great cardiac vein flow was 68 ± 11 ml/min (range, 51 to 78 ml/min) or 65 ± 10% of the coronary sinus blood flow. The method allowed continuous measurement of flow over a period of severa...

Measurement of Coronary Sinus Blood Flow by Continuous Thermodilution in Man

The myocardium is able to utilize both carbohydrates and noncarbohydrates for the performance of its work (1). Extraction of an individual substrate is usually determined by its arterial level. Thus, after a carbohydrate meal the heart derives much of its energy from the metabolism of carbohydrates; however, in the fasting state myocardial energy production is dependent upon noncarbohydrates, primarily fatty acids (1). Recent studies (2, 3) have shown that the principal lipid fraction of plasma concerned with the transport and metabolism of fatty acids is the plasma nonesterified or free fatty acid (FFA) fraction. Previous studies have already demonstrated that the heart uses a considerable amount of FFA (3). The present study was undertaken to determine further the role of fatty acids in myo-cardial metabolism. Most of the methods used in this investigation have been described in detail in previous studies from this laboratory. Coronary sinus blood was obtained from a catheter placed in the coronary sinus, and blood samples from metabolic studies were simultaneously obtained from arterial and coronary sinus blood (1). The coronary blood flow was determined with the nitrous oxide desaturation method (4). Blood glucose was determined by the method of Hagedorn and Jensen (5) using Somogyi's method to prepare the blood filtrate (6).

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Myocardial metabolism of fatty acids.

The tissue content of energy-rich phosphates and glycolytic metabolites and the activity of myocardial enzymes were examined in the dog after producing myocardial infarction by ligating branches of the anterior descending and circumflex coronary arteries. The pattern of systolic fiber movement shown by a strain-gauge assembly differentiated ischemic from nonischemic portions of myocardium. In ischemic muscle, 30 minutes after onset of ischemia, creatine phosphate content fell from 8.0 to 1.4 µmoles/g, ATP content fell from 5.8 to 1.5 µmoles/g, lactate content rose tenfold, and α-glycerophosphate content rose fivefold. The content of energy-rich phosphates and glycolytic metabolites did not change much in nonischemic muscle. The activities of myocardial enzymes were assayed in extracts of tissue samples from ischemic and nonischemic muscle 5 to 120 minutes after coronary artery occlusion. The activities of aldolase, lactic dehydrogenase (LDH), glyceraldehydephosphate dehydrogenase, α-glycerophosphate dehydrogenase, malate dehydrogenase (MDH), and 6-phosphogluconate dehydrogenase did not change significantly in ischemic muscle during 2 hours of observation. In nonischemic muscle, phosphofructokinase activity increased 75% 5 minutes after coronary occlusion, followed by an increase in activity of isocitrate dehydrogenase, creatinephosphokinase, MDH, and LDH. The enzymatic changes in nonischemic muscle suggest metabolic changes in nonischemic muscle accompanying compensatory hyperfunction and increased energy requirements of surviving muscle.

Early Changes in Energy Metabolism in the Myocardium Following Acute Coronary Artery Occlusion in Anesthetized Dogs

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Extraction and release of individual free fatty acids by the heart and fat depots.

The action of sublingual nitroglycerin (0.6 mg) and intravenous propranolol (0.1 mg/kg) on shortening of right ventricular fibers was investigated in patients with and without coronary artery disease. This was accomplished with a newly devised strain gauge catheter. Hemodynamic parameters and changes in the oxidation-reduction potential of heart muscle were determined. Nitroglycerin results in decrease in shortening and velocity of shortening of ventricular fibers, heart rate, left ventricular end-diastolic and systemic pressure, dp/dt, tension-time index, stroke index, peripheral resistance, and left ventricular minute work in normal and arteriosclerotic subjects. Intravenous propranolol leads to a fall in velocity of shortening of myocardial fibers, heart rate, dp/dt, stroke index, and left ventricular minute work. However, there is an increase in tension-time index and peripheral resistance with no change in systemic pressure. Left ventricular end-diastolic pressure rises significantly in arteriosclero...

A Comparative Study of Nitroglycerin and Propranolol

The coincidence counting technic was used to measure the clearance equivalent of rubidium-84 as a function of coronary flow by the human heart in vivo. This technic makes possible a distinction of radioactivity of the heart muscle from the surrounding tissue, eliminates lead collimation, and is more sensitive than the singles technic. In experiments on isolated dog heart it was found that changes in rate of perfusion of the coronary arteries failed to influence the myocardial extraction ratio of rubidium-84. Alterations in heart rate were also without effect. Nitroglycerin increased the clearance equivalent of rubidium-84 in patients without coronary heart disease. In patients with coronary artery disease the drug led to fall in clearance equivalent. The method has been helpful in distinguishing between normal individuals and those with coronary artery disease.

Richard J. Bing

Papers

Myocardial metabolism of fatty acids.

Early Changes in Energy Metabolism in the Myocardium Following Acute Coronary Artery Occlusion in Anesthetized Dogs

Extraction and release of individual free fatty acids by the heart and fat depots.

A Comparative Study of Nitroglycerin and Propranolol

The Determination of Coronary Flow Equivalent with Coincidence Counting Technic