[Osteoid osteoma in the scaphoid bone as cause of radiocarpal pain in a 15-year-old patient]. / Osteoidosteom im Os scaphoideum als Ursache für radiokarpale Handgelenksbeschwerden bei einem 15-jährigen Patienten.

Osteoid osteomas are benign bone tumors which rarely occur in the hand and impose severe diagnostic problems. The course of the disease is often protracted before the patient receives an adequate surgical treatment. The case of an osteoid osteoma in the scaphoid bone of a 15-year-old patient is presented, who was completely symptom free after a true diagnostic odyssey by resection of the nidus and reconstruction by crest bone graft and spongiosaplasty.

[Fatal hyperpyrexia in an adolescent patient with severe burns after a traffic accident]. / Letale Hyperpyrexie bei einem jugendlichen Schwerbrandverletzten nach Verkehrsunfall.

After a motorcycle accident a 16-year-old patient suffered severe burns to 40.5 % of the total body surface area (TBSA) of which 37 % were deep subdermal burns. After tangential and partly epifascial necrosectomy, Integra® was used as a temporary dermis replacement material for the lower extremities, combined with extensive negative pressure wound therapy (NPWT). In the further course of the treatment the patient developed uncontrollable hyperpyrexia with a fatal outcome. Possible influencing factors, such as the dermis replacement material combined with NPWT over large areas as well as the differential diagnoses propofol infusion syndrome, heatstroke and malignant hyperthermia are discussed.

[Pyoderma gangrenosum following AICD implantation: differential diagnosis to necrotizing fasciitis]. / Pyoderma gangraenosum nach AICD-Implantation: Differenzialdiagnose zur nekrotisierenden Fasziitis.

Pyoderma gangrenosum is rarely seen in the surgical disciplines. In the described case the patient was initially diagnosed with necrotizing fasciitis and admitted to the intensive care unit suffering from septic shock. The automated implantable cardioverter defibrillator (AICD), the suspected focus for infection, had already been removed. Following weeks of broad spectrum antibiotics and wound debridement without clinical improvement the alternative diagnosis of pyoderma gangrenosum was reached. Consequently the patient was treated with immunosuppressive therapy and his condition improved rapidly such that he was ultimately discharged to rehabilitation.

Volatile metal complexes.

Fundamental investigations of the chemical and physical properties of metal beta-diketonate complexes have revealed unusual volatility, as well as solvolytic and thermal stability and solubility in organic solvents. Certain general rules describing the volatility of metal beta-diketonates on the basis of ligand shell character and metal ion size have arisen from extensive gas chromatographic and vapor pressure studies. Several practical applications of volatile beta-diketonates teke advantage of their special properties. In ultratrace metal analysis by gas chromatography, use of these chelates has allowed the detection of smaller amounts of certain metals than can be detected by any other analytic method. Certain rare earth beta-diketonates have been found useful as antiknock additives in gasoline and as catalysts for the removal of carbonaceous deposits from the combustion chambers of internal combustion engines.

Nicotine does not influence arterial lipid deposits in rabbits exposed to second-hand smoke.

BACKGROUND: Second-hand smoke (SHS) accelerates atherogenesis and impairs vascular function. The role of nicotine in this process has not been defined. METHODS AND RESULTS: To examine the potential effects of nicotine on atherogenesis and vascular function, 48 rabbits receiving a 0.5% cholesterol diet were randomized to control (cholesterol diet only), SHS from nicotine-standard research cigarettes (SHS-ST), and SHS from nicotine-free research cigarettes (SHS-NF). The SHS rabbits were exposed to 48 nicotine-standard (12 animals) or nicotine-free (12 animals) cigarettes/d, 5 d/wk for 10 weeks. Air carbon monoxide and particulates and plasma carboxyhemoglobin were significantly higher in the 2 SHS groups than the control group (P<0.001). The SHS-ST group had significant increases in plasma nicotine and cotinine compared with the other groups (P<0.001). There was no difference in serum lipids. Lipid lesions were increased in both SHS groups (54+/-5% [SEM] aorta and 66+/-4% pulmonary artery, 53+/-7% and 69+/-4%, and 39+/-4% and 43+/-3% in the SHS-ST, SHS-NF, and control groups, respectively; P=0.049 aorta and P<0.001 pulmonary artery). CONCLUSIONS: SHS exposure increased arterial lipid lesions, but nicotine did not contribute significantly to this effect. This effect is presumably due to other combustion products in the smoke.

Verapamil prevents the development of alcoholic dysfunction in hamster myocardium.

Ethanol causes depression of cardiac function. A new model in hamsters was developed for studying ethanol-induced myocardial dysfunction and the effects of verapamil in preventing the functional and metabolic derangements caused by ethanol ingestion were evaluated. Ethanol was added to the drinking water of hamsters in increasing amounts, reaching 50% from 5 weeks on. A control group received plain water only. A third group had verapamil (1.75 mg/cc) added to the ethanol-water mixture to evaluate its potential protective effect. After 5, 7 and 12 weeks, the animals were killed and the hearts perfused using a Langendorff heart preparation. Pressures were recorded and metabolic analysis was performed by the freeze-clamp technique. Compared with control hearts, the hearts from hamsters ingesting ethanol showed significant depression of developed pressure and maximal rate of rise in pressure. There was also significant depression of high energy phosphates and adenosine. The animals drinking the ethanol-verapamil mixture had preservation of left ventricular performance and high energy phosphates, with measurements indistinguishable from those of the control group. In summary, verapamil prevented the development of myocardial depression and preserved normal energy metabolism in hearts of hamsters drinking 50% ethanol.

Regression of atherosclerosis in cholesterol-fed rabbits: effects of fish oil and verapamil.

Previous studies have shown that either fish oil or verapamil can attenuate the development of atherosclerosis in the lipid-fed rabbit. The present study was designed to evaluate the individual and combined effects of these two interventions on regression. Seventy New Zealand rabbits in seven groups (10 each) were fed a 0.3% cholesterol diet for 10 weeks. Control group C10 was then killed. Control group C20 was fed a 0.3% cholesterol diet and the other five groups were fed a normal diet for an additional 10 weeks. Group F in three treated groups received 2 ml/day of fish oil (Proto-Chol, eicosapentaenoic acid, 180 mg/ml and docosahexaenoic acid, 120 mg/ml) by gavage. Group V received verapamil, 2 g/1,000 ml drinking water, and group FV received both fish oil and verapamil for an additional 10 weeks. Group CF (control for fish oil) received 2 ml/day of water by gavage and group CV (control for verapamil) received water without gavage for an additional 10 weeks. The percent of aortic and pulmonary atherosclerosis was measured by planimetry of sudanophilic lesions. The percent of aortic lesions in the four control groups (C20, C10, CF and CV) was 57 +/- 22, 40 +/- 15, 40 +/- 14 and 33 +/- 25%, respectively. The fish oil or verapamil groups (F, V, FV) showed a significant reduction in aortic lesions: 15 +/- 17%, p less than 0.05; 16 +/- 12%, p less than 0.05; and 26 +/- 24%, p = NS, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibition of atherosclerosis by fish oil in cholesterol-fed rabbits.

To evaluate the effects of dietary fish oil on cholesterol-induced atherosclerosis, 36 New Zealand rabbits in four groups were fed a 0.3% cholesterol diet for 10 weeks. One group served as control, whereas groups I, II and III received 1, 2 and 3 ml/day, respectively, of fish oil (Protochol, eicosapentaenoic acid, 180 mg, and docosahexaenoic acid [DHA], 120 mg/ml). The percent of aortic and pulmonary atherosclerosis was measured by planimetry of sudanophilic lesions. The percent of aortic lesions in the control group was 59 +/- 22%. The two higher dose fish oil groups showed a significant reduction in aortic lesions: group I (40 +/- 26%, p = NS), group II (18 +/- 11%, p less than 0.01) and group III (36 +/- 22%, p less than 0.05). Area of pulmonary artery lesions was significantly higher in the control group (48 +/- 22%) as compared with group I (15 +/- 13%, p less than 0.01), group II (4 +/- 3%, p less than 0.01) and group III (8 +/- 9%, p less than 0.01). The high cholesterol diet in the control group decreased bleeding time from 82 +/- 17 to 59 +/- 22 s (p less than 0.05). Groups II and III showed an increased bleeding time (62 +/- 15 to 84 +/- 17 s and 66 +/- 22 to 95 +/- 27 s; p less than 0.05, respectively). Fish oil did not significantly alter total serum cholesterol and high density lipoprotein (HDL) cholesterol. In group II triglyceride decreased from 128 +/- 22 to 64 +/- 25 mg/dl (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Passive smoking increases experimental atherosclerosis in cholesterol-fed rabbits.

OBJECTIVES: We evaluated the influence of passive smoking on experimental atherosclerosis in cholesterol-fed rabbits. BACKGROUND: Exposure to environmental tobacco smoke (ETS) has been epidemiologically linked to death from ischemic heart disease in nonsmokers. METHODS: New Zealand male rabbits were randomly divided into three groups after 2 weeks of a 0.3% cholesterol diet. Sixteen rabbits were exposed to a high and 16 rabbits to a low dose of ETS; 32 rabbits located in another room served as an unexposed control group. After 10 weeks of ETS exposure, all rabbits were killed, and the percent of aortic and pulmonary artery endothelial surfaces covered by lipid lesions was measured by staining and planimetry. RESULTS: Average air nicotine, carbon monoxide and total particulate concentrations were 1,040 micrograms/m3, 60.2 ppm and 32.8 mg/m3 for the high dose ETS group, 30 micrograms/m3, 18.8 ppm and 4.0 mg/m3 for the low dose ETS group and < 1 microgram/m3, 3.1 ppm and 0.13 mg/m3 for the control group. The percent atherosclerotic involvement of the aorta and pulmonary artery increased significantly with ETS exposure (for the aorta, 30 +/- 19% [mean +/- SD] for the control group, 36 +/- 14% for the low dose ETS group and 52 +/- 21% for the high dose ETS group, p < 0.001; for the pulmonary artery, 22 +/- 15% for the control group, 29 +/- 25% for the low dose ETS group, and 45 +/- 12% for the high dose ETS group, p < 0.001). Bleeding time was significantly shorter in the two ETS groups than in the control group (86 +/- 17 vs. 68 +/- 15, 68 +/- 18 s, p < 0.001). There were no significant differences in serum triglycerides, cholesterol and high density lipoprotein cholesterol at the end of the study. CONCLUSIONS: Environmental tobacco smoke affects platelet function and increases aortic and pulmonary artery atherosclerosis. This increase of atherosclerosis was independent of changes in serum lipids and exhibited a dose-response relation. These results are consistent with data from epidemiologic studies demonstrating that ETS increases the risk of death due to heart disease.

Quantitation of regional myocardial function by cine computed tomography: pharmacologic changes in wall thickness.

To determine the capability of high speed computed transmission tomography to quantitate regional wall thickening dynamics over a wide range of physiologic states, left ventricular wall thickening was studied in nine anesthetized mongrel dogs in the control state and during separate infusions of dobutamine (10 micrograms/kg per min) and phenylephrine (25 micrograms/kg per min). After an intravenous bolus of contrast medium the heart was imaged from base to apex with serial transverse images in eight short-axis cine computed tomographic planes. In each dog during each experimental condition, 50 ms scans spanning the cardiac cycle were acquired at each anatomic level. Left ventricular epicardial and endocardial boundaries were identified on end-diastolic and end-systolic images at the equatorial left ventricular planes by an objective threshold contour method validated in a series of experiments performed on ex vivo anatomic specimens. End-diastolic and end-systolic frames were automatically realigned by superposition of epicardial centers of gravity and then rotated using a cross correlation function. The left ventricular wall thickness was measured manually at 16 points around the circumference by two independent observers. For the group of dogs the average percent wall thickening was 40.5 +/- 28.2% and varied among segments from 18 to 70% in the control state. After dobutamine was administered, significant increases in heart rate and cardiac output (p less than or equal to 0.01) were accompanied by an increase in the average wall thickening (73.6 +/- 51.2%; p less than or equal to 0.001) in the left ventricle; the average wall thickening among segments ranged from 46 to 97%. After phenylephrine administration, significant increases in mean blood pressure and cardiac output (p less than or equal to 0.01) were noted along with a significant increase in average left ventricular wall thickening (60.3 +/- 52.5%; p less than or equal to 0.001). Despite an overall increase in the percent wall thickening, no statistically significant changes in segmental contraction pattern between control and drug intervention states were observed. The wall thickness measurements were highly reproducible between the two independent readers (reliability coefficient = 0.99). Cine computed tomography-derived measurements can potentially be used for quantitative assessment of left ventricular wall thickening dynamics of a single heartbeat during acute interventions, such as the administration of drugs.

Ventricular diastolic pressure-volume shifts during acute ischemic left ventricular failure in dogs.

Ischemic left ventricular failure was produced in eight acutely instrumented, anesthetized dogs to study the contribution of changing myocardial compliance and pericardial pressure to shifts in right and left ventricular diastolic pressure-volume relations. Right and left ventricular and pericardial volumes were measured by ungated computed tomography. Cardiac volumes were manipulated by infusion of saline solution, hemorrhage, phenylephrine infusion and, during failure only, nitroglycerin administration. During both control and failure periods, these interventions shifted the left and right ventricular pressure-volume relations by changing pericardial pressure only; that is, these interventions caused no change in the ventricular transmural pressure-volume relation. The induction of failure as such increased pericardial pressure only minimally and did not change the left ventricular or right ventricular transmural pressure-volume relations significantly. Volume loading during the control period caused an apparent pericardial creep which attenuated the pericardial effect on ventricular pressure-volume relations. During failure, volume loading caused an increase of right ventricular volume, but tended to decrease left ventricular volume; this was associated with a leftward displacement of the interventricular septum. In conclusion, in the presence of ischemic left ventricular failure as well as normally, changes in preload, afterload and circulating blood volume shift ventricular diastolic pressure-volume relations by stretching or relaxing the pericardium, thus changing pericardial pressure. In these circumstances, there were no consistent changes in myocardial compliance.

Verapamil suppresses atherosclerosis in cholesterol-fed rabbits.

The effect of verapamil, a drug that reduces the concentration of intracellular calcium, on atherogenesis was evaluated in rabbits fed a cholesterol-rich diet for 10 weeks. Ten rabbits received oral verapamil, 8 mg/kg daily; eight received the same oral dose and 0.5 mg/kg daily subcutaneously; nine received oral lanthanum, 35 mg/kg daily, and nine were controls. Over the 10 week period, all groups had average serum cholesterol levels greater than 1,500 mg/dl (normal = 90 +/- 63 mg/dl). At the end of the experiment, the aortas were removed, opened and stained for lipid with Sudan IV. The extent of atherosclerosis was determined by planimetry. The group receiving oral and parenteral verapamil had significantly less atherosclerosis (25 +/- 26% of total intimal area; mean +/- standard deviation), as compared with the controls (73 +/- 24%). Reduction of atherosclerosis with oral verapamil (51 +/- 22%) and lanthanum (59 +/- 31) was not statistically significant. Indexes of contractility in isolated right ventricular papillary muscles (developed tension at maximal length [Lmax] and maximal velocity of shortening [Vmax]) were reduced in the group treated with oral and parenteral verapamil, but not in the others. It is concluded that verapamil suppresses the development of atherosclerosis in rabbits fed a cholesterol-rich diet.

Comparative effects of pretreatment with captopril and losartan on cardiovascular protection in a rat model of ischemia-reperfusion.

OBJECTIVES: We sought to assess the comparative effects of pretreatment with captopril and losartan on myocardial infarct size and arrhythmias in a rat model of ischemia-reperfusion. BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) inhibit the renin-angiotensin system in different ways. However, the comparative effects of pretreatment with ACE inhibitors or ARBs on acute myocardial infarct size and arrhythmias are unknown. METHODS: We randomly assigned 117 female Sprague-Dawley rats into three groups: group N was the normal control; group C was given 40 mg/kg body weight per day of captopril in drinking water; and group L was given 40 mg/kg per day of losartan in drinking water. After 10 weeks of pretreatment, 25 rats in each group were subjected to 17 min of left anterior descending coronary artery occlusion and 2 h of reperfusion with hemodynamic and electrocardiographic monitoring. Fourteen rats in each group had blood samples drawn and aortic rings removed to study vascular reactivity. RESULTS: Mortality during ischemia and reperfusion was lower in combined groups L and C than in group N (4.2% vs. 19.2%, p = 0.042). Rats treated with losartan had significantly higher levels of angiotensin II in their plasma. Hemodynamic variables were not significantly different among the three groups. The thresholds of ventricular fibrillation (VF) before occlusion and after reperfusion were significantly higher in groups L and C than in group N (1.99 +/- 0.24 and 1.93 +/- 0.27 vs. 1.23 + 0.17 mA, p = 0.04; 2.13 +/- 0.25 and 1.78 +/- 0.22 vs. 0.95 +/- 0.11 mA, p = 0.001). The average episodes of ventricular tachycardia (VT) and VF per rat were significantly less in groups L and C than in group N (0.96 +/- 0.2 and 1.2 +/- 0.3 vs. 2.8 + 0.4 mA, p < 0.001). Myocardial infarct size was significantly smaller in groups L and C than in group N (34 +/- 3% and 35 +/- 3% vs. 44 +/- 3%, p = 0.031, 0.043). Endothelium-dependent vasorelaxation induced by a calcium ionophore (A23187) was increased in both groups but was only statistically significant in group C (p = 0.020). CONCLUSIONS: Losartan and captopril have similar cardiovascular protective effects in a rat model of ischemia-reperfusion. They increased the threshold of VF, decreased mortality and decreased episodes of VT and VF, as well as decreased myocardial infarct size.

Testosterone worsens endothelial dysfunction associated with hypercholesterolemia and environmental tobacco smoke exposure in male rabbit aorta.

OBJECTIVES: To assess the effects of interaction of sex hormones, hypercholesterolemia (HC) and environmental tobacco smoke (ETS) exposure on endothelium-dependent relaxation, we examined vascular reactivity in vitro in an animal model of atherogenesis. BACKGROUND: Animal and human studies indicate the presence of interactions between classic coronary artery disease risk factors and endothelium-dependent relaxation. Sex hormones have also been shown to influence release of endothelium-derived relaxing factor. METHODS: New Zealand White rabbits were randomized to receive either an HC diet (n = 8) or ETS exposure plus HC diet (n = 8). Eight rabbits receiving a normal diet, without exposure to ETS, served as the control group. The HC diet consisted of 3% soybean oil and 0.3% cholesterol by weight over 13 weeks. The source of ETS was sidestream smoke of 4 cigarettes/15 min, 6 h/day, 5 days/week over 10 weeks in a smoking chamber. Rabbits were killed, and fresh aortic rings were harvested and maintained in oxygenated Krebs solution in an organ bath at 37 degrees C. Rings were precontracted with norepinephrine and exposed to acetylcholine in increasing doses, and isometric tension was recorded. Rings were also exposed to physiologic concentrations (1 nmol/liter) of either 17-beta-estradiol, testosterone or progesterone before pre-contraction with norepinephrine and relaxation with acetylcholine. Endothelium-independent relaxation was studied using nitroglycerin. The surface area of the ring covered by lipids was measured by Sudan IV staining. RESULTS: HC and ETS significantly reduced endothelium-dependent relaxation (p = 0.01 and p < 0.0005, respectively) and caused atherogenesis (p < 0.0005 and p = 0.047, respectively) but did not affect endothelium-independent relaxation. Incubation with estradiol and estradiol plus progesterone did not influence endothelium-dependent relaxation. Testosterone reduced endothelium-dependent relaxation (p = 0.049) and augmented the endothelial dysfunction associated with ETS exposure and HC (p = 0.03). CONCLUSIONS: Both HC and ETS are atherogenic and impair endothelial function but do not affect endothelium-independent relaxation. Physiologic levels of estradiol and estradiol plus progesterone do not affect endothelium-dependent relaxation. Physiologic levels of testosterone impair relaxation and augment the endothelial dysfunction associated with ETS exposure and HC.

Effects of second-hand smoke and gender on infarct size of young rats exposed in utero and in the neonatal to adolescent period.

OBJECTIVES: We sought to assess the effects of second-hand smoke (SHS) and gender on infarct size in young rats exposed in utero or in the neonatal to adolescent period, or both. BACKGROUND: We previously demonstrated that exposure to SHS increases infarct size in a rat model of ischemia and reperfusion, with a dose-response relation. These results are consistent with epidemiologic studies demonstrating that SHS increases risk of death from heart disease. METHODS: Thirty-one pregnant female rats were randomly divided into two groups: those exposed to SHS and a control group (non-SHS). After 3 weeks, each rat had given birth to 10 to 12 rats. One hundred one neonatal rats were divided into four groups according to exposure to SHS in utero (SHSu) and randomized to SHS exposure in the neonatal to adolescent period (SHSna). After 12 weeks, all rats were subjected to 17 min of left coronary artery occlusion and 2 h of reperfusion. RESULTS: Birth mortality was higher in the SHSu group than in the non-SHSu group (11.9% vs. 2.8%, p < 0.001). Body weight of neonatal rats at 3 and 4 weeks in the two SHSu groups was lower than that of rats in the two non-SHSu groups (p < 0.001). Exposure to SHSna increased endothelin-1 levels in plasma (p = 0.001). In all 70 young rats who survived the neonatal period, infarct size (Infarct mass/Risk area x 100%) was greater in the SHSna groups than in the non-SHSna groups (p = 0.005) and in the male groups than in the female groups (p < 0.001). CONCLUSIONS: Exposure to SHS in the neonatal to adolescent period and male gender increased myocardial infarct size in a young rat model of ischemia and reperfusion. These results are consistent with epidemiologic studies demonstrating that SHS increases the health risk to neonates and adolescents.

Cardiomyopathic and healthy acidotic hamster hearts: mitochondrial activity may regulate cardiac performance.

A 50% decrease in adenine nucleotides and a 60% decrease in adenosine triphosphate concentration was found in glucose perfused myopathic Syrian hamster heart (240 days old) whereas there was an 18% decrease and 40% decrease respectively in acidotic healthy Syrian hamster heart re-equilibrated with a physiological medium. Correspondingly, there was a 60% decrease in cardiac performance with both models. Developed pressure fell when the phosphorylation potential decreased to less than or equal to 2; however, the heart recovered if mitochondrial activity was activated. If a substrate such as pyruvate or ribose was used with either model cardiac performance returned to near normal, although adenine nucleotide and adenosine triphosphate concentrations were further depressed. With glucose as substrate cardiomyopathic hearts, healthy acidotic hearts, and healthy acidotic hearts re-equilibrated with glucose as substrate had low pyruvate concentrations; limited availability of pyruvate depressed mitochondrial activity. Like the myopathic hearts the re-equilibrated acidotic hearts had high myocardial pyruvate concentrations, above normal ratios of phosphocreatine to creatine, and near normal oxygen consumption, developed pressure, dP/dt, and cyclic adenosine monophosphate concentrations when re-equilibrated with a medium containing pyruvate or ribose as substrate, although adenosine triphosphate and adenine nucleotide concentrations were severely depressed. When adenosine triphosphate values fell from 24 to 2 mumol X g-1 dry weight in the pyruvate or ribose perfused and normal functioning heart the heart stopped beating with no progressive fall in performance before termination of the metabolic processes.

Myocardial protection with verapamil during ischaemia and reperfusion: dissociation between myocardial salvage and the degree of ATP depletion during ischaemia.

STUDY OBJECTIVE: The aim was to evaluate the protective effect of verapamil during myocardial ischaemia and reperfusion. DESIGN: In vivo phosphorus-31 (31P) magnetic resonance spectroscopy was performed on rats pretreated with verapamil (mg.kg-1 intraperitoneal) and controls during a 45 min left coronary artery occlusion and 60 min reperfusion. In separate groups of animals, haemodynamic measurements were taken at baseline, during ischaemia, and during reperfusion. Infarct size was determined by staining with triphenyltetrazolium chloride. EXPERIMENTAL MATERIAL: Female Sprague-Dawley rats were used (control group n = 25, experimental group n = 24). MEASUREMENTS AND MAIN RESULTS: Infarct size was significantly reduced in the verapamil group compared to controls: 9.9(SEM 2.3)%, n = 19 v 28.5(2.7)%, n = 19, p less than 0.001 (infarct % of left ventricular mass). Myocardial phosphocreatine and ATP levels were reduced to similar levels in both verapamil and control animals after 45 min ischaemia: 56.8(3.4)%, n = 10, v 61.4(1.8)%, n = 11 NS; 67.7(2.7)%, n = 10 v 69.7(2.9)%, n = 11, NS (% of baseline value). After 60 min reflow, there was significant recovery of phosphocreatine [91.1(4.2)% of baseline, p less than 0.05] and ATP [86.8(2.7)% of baseline, p less than 0.05] in the verapamil group, but no recovery of high energy phosphates in controls [66.3(2.8), NS; 69.6(2.7), NS]. The left ventricular systolic pressure, heart rate, rate-pressure product, and maximum rate of left ventricular pressure development were similar prior to ischaemia, and during ischaemia in both groups. There was an inverse correlation between infarct size and the degree of phosphocreatine recovery after 60 min of reperfusion (PCr recovery (%) = -0.99 x infarct size (%) + 101; r = 0.91; p less than 0.01; n = 14). Furthermore, in a separate group of animals (n = 9), there was a significant correlation between the size of the ischaemic area at risk and the degree of phosphocreatine decline after 15 min of coronary occlusion (PCr reduction (%) = 0.91 x risk area (%) + 5.6; r = 0.97; p less than 0.01). CONCLUSIONS: Pretreatment with verapamil extends the ischaemic time after which reperfusion results in myocardial salvage in this model of ischaemia and reperfusion. This protective effect is independent of the haemodynamic determinants of myocardial oxygen demand and the degree of ATP and phosphocreatine depletion during the ischaemic period. In this model of reversible ischaemia, 31P magnetic resonance spectroscopy is useful for quantitating both the size of the ischaemic region during coronary artery occlusion and infarct size after reperfusion.

A new apex-ejecting perfused rat heart preparation: relation between coronary flow and loading conditions.

The isolated perfused rat heart is an important experimental preparation for both mechanical and biochemical studies. In order to define better the relationship between coronary flow and loading conditions, a new preparation was developed in which the left ventricle ejected through the apex, while the aortic perfusion pressure could be separately controlled at a higher level than the apex afterload. Results were compared with a standard aortic perfused and ejecting preparation. All analyses were made at low calcium concentration (1.6 mmol X litre-1) for reducing cardiac performance. Coronary flow was related to perfusion pressure in the aortic ejecting preparation when the aortic afterload chamber was between 6.0 and 9.3 kPa (45 and 70 mmHg). Coronary autoregulation was demonstrable in the apex ejecting preparation irrespective of the height of the apex afterload chamber and the aortic ejecting preparation when the aortic chamber was between 11.0 and 16.0 kPa (83 and 120 mmHg). Following the addition of 10(-6) mol X litre-1 adenosine, there was significant coronary vasodilatation, and flow became pressure dependent in all cases. In the apex-ejecting preparation, with a high aortic pressure, coronary flow remained at relatively fixed level, and increases in oxygen demand were met by increasing oxygen extraction. Thus, in this preparation oxygen extraction was directly related to workload. With abrupt increases in afterload, going from 6.0 to 9.3 kPa (45 to 70 mmHg) to a higher level, there was evidence of transient hypoxia with the aortic ejecting but not the apex ejecting preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Verapamil, propranolol, and hydralazine protect against the acute cardiac depression induced by adriamycin.

The apex ejecting isolated rat heart perfused with media containing 3 X 10(-5) mol . litre-1 adriamycin for 40 min demonstrated the following changes in contraction patterns: (a) a ten-fold increase in end-diastolic pressure; (b) a 45% decrease in developed pressure; (c) a 17% decrease in coronary flow; (d) a 27% increase in time to peak pressure; (e) a 26% increase in time for pressure to fall 50% during relaxation; and (f) a 65% decrease in maximum (+) and (-) dP/dt. In rats pretreated 1 h before death, verapamil, propranolol, and hydralazine significantly attenuated the cardiac depression produced by adriamycin. The combinations of verapamil and hydralazine, or propranolol and hydralazine were especially efficacious. Particularly striking was the protection afforded against an increase in diastolic pressure. Digoxin pretreatment afforded no protection. It is postulated that the acute depressive effects of adriamycin may be related to calcium overload.