Cardiac re-synchronization therapy: effects on myocardial perfusion at rest, after vasodilation and oxygen consumption.

AIM: Cardiac resynchronization therapy (CRT) has been shown to improve haemodynamics and clinical symptoms in heart failure patients. The present study evaluated the effects of a 4-month CRT on myocardial blood flow (MBF) at rest, after vasodilation and on myocardial oxygen consumption (MVO(2)). PATIENTS, METHODS: We studied 16 patients with idiopathic dilated cardiomyopathy prior to and during CRT performed as biventricular pacing. Resting MBF and MVO(2) were determined from an (11)C-acetate PET study and vasodilator MBF from a (13)N-ammonia study. RESULTS: MBF at rest (0.55 +/- 0.10 ml/min/g), after vasodilation (1.20 +/- 0.45 ml/min/g), and MVO2 (0.082 +/- 0.014/min) did not change by mid-term CRT at a global level (0.57 +/- 0.11 ml/min/g; 1.32 +/- 0.49 ml/min/g; 0.085 +/- 0.018/min), whereas the rate pressure product (RPP) normalised MVO(2) decreased from 0.104 +/- 0.024 to 0.086 +/- 0.018/min (p = 0.02). At baseline, the regional analysis revealed significantly higher values for all parameters in the lateral wall than for those in the other walls. Under CRT the regional differences between the resting parameters equalized and all parameters showed significant lower coefficients of variation. CONCLUSION: Effects of mid-term CRT on resting MBF, vasodilator MBF and MVO(2) occur at a regional level. The resynchronization is associated with a more homogenous distribution pattern of these parameters among the myocardial walls. Substantial alterations to global MBF at rest, after vasodilation or to MVO(2) are not detectable. Regarding the RPP normalised MVO(2), there is evidence of improved ventricular efficiency through CRT.

[Myocardial perfusion under H.E.L.P. -apheresis. Objectification by PET]. / Myokardiale Perfusion unter H.E.L.P.-Apherese. Objektivierung durch PET.

Due to endothelial dysfunction (ED), coronary vasodilation capacity is reduced in patients with hypercholesterolemia. Cholesterol lowering may largely restore endothelial function. Currently, it is supposed that the onset of this therapeutic effect takes weeks or even months. However, by means of LDL apheresis, a significant LDL reduction may be achieved within hours. Dynamic quantitative positron emission tomography (PET) performed before and after LDL apheresis showed that mean global myocardial perfusion can be measured at rest and after pharmacological vasodilation with dipyridamole using N13 ammonia as tracer.A total of 35 patients (11 women and 24 men) with documented coronary heart disease and hypercholesterolemia underwent PET immediately prior to LDL apheresis and 18-20 hours thereafter. In addition to the decrease in LDL cholesterol (from 175+/-50 to 77+/-25 mg/dl) and fibrinogen (from 287+/-75 to 155+/-52 mg/dl), a significant improvement of myocardial blood flow under dipyridamole (177+/-59 vs 217+/-82 ml/min 100 g, p<0.0001), of coronary flow reserve (2.10+/-0.82 vs 2.62+/-1.02, p<0.0001) and of minimal coronary resistance (0.56+/-0.20 vs 0.44+/-0.17 mmHg 100 g min/ml, p<0.0001) were achieved. Plasma viscosity decreased only by 7.8%. Within 20 hours after single LDL apheresis a 20% improvement of coronary vasodilation capacity was noninvasively demonstrated and quantified.

Improvement in coronary flow reserve determined by positron emission tomography after 6 months of cholesterol-lowering therapy in patients with early stages of coronary atherosclerosis.

BACKGROUND: Early stages of coronary atherosclerosis are characterized by a mainly functional impairment of coronary vasodilator capacity under the impact of such risk factors as hypercholesterolemia. The goal of this study was to determine whether 6-month cholesterol-lowering therapy improves coronary flow reserve in patients with angina, reduced flow reserve despite minimally diseased coronary vessels or even normal angiogram, and mild to moderately elevated LDL levels on average. METHODS AND RESULTS: We noninvasively investigated 23 consecutive patients (18 men, 5 women; mean age, 56+/-7.6 years) with a mean LDL level of 165+/-34 mg/dL at baseline by PET for myocardial blood flow measurement with [13N]ammonia at rest and under dipyridamole stress (0.56 mg/kg) before and after lipid-lowering therapy with simvastatin for 6 months. Between baseline and the 6-month follow-up, total cholesterol concentration fell from 241+/-44 to 168+/-34 mg/dL, and the LDL level decreased from 165+/-34 to 95+/-26 mg/dL (P<0.001). Overall, coronary flow reserve increased from 2.2+/-0.6 to 2.64+/-0.6 (P<0.01). Maximal coronary flow increased significantly from 182+/-36 to 238+/-58 mL/minx100 g (P<0.001) at follow-up. Minimum coronary resistance declined significantly from 0. 51+/-0.12 to 0.40+/-0.14 mm Hg. mL-1. minx100 g (P<0.001). Concomitantly, a regression of anginal symptoms was observed in most patients. CONCLUSIONS: Our results suggest that cholesterol-lowering therapy with simvastatin may improve overall coronary vasodilator capacity assessed noninvasively by PET in patients with mild to moderate hypercholesterolemia. Consequently, intensive lipid-lowering therapy is considered a vasoprotective treatment for selected patients in very early stages of coronary atherosclerosis with the potential of preventing further disease progression.

[Changes in life style as a causal therapeutic approach in coronary heart disease]. / Lebensstiländerung als kausaler Therapieansatz der koronaren Herzkrankheit.

Life style measures (weight reduction and control, reduction of total fat calories to < 30% of total calories, modification of fat intake to increased monounsaturated vegetable fat, increased intake of dietary fibers, increased physical activity, controlled stress relaxation) are the basis of longterm therapy of coronary heart disease. For transformation to daily life both patient and doctor need motivation, information, patience, and realistic aims. For realization the 10 rules of medical information should be followed. The patient must be informed that the "new lifestyle" is not punishing but means a new quality of life. With respect to the most important metabolic syndrome with hyperinsulinemia due to insulin resistance, weight reduction is the most important measure for preventing complications of atherosclerosis. The patient should use a diary for weight control and blood pressure self-measurement. Secondary prevention of CHD has been shown useful and effective; however, most patients need additionally drug therapy to avoid or retard progression of the coronary heart disease. The targets for cholesterol and blood pressure control are low; the responsibility of the patient remains high. Besides weight reduction, stopping smoking, lowering lipids, controlling hypertension, and aspirin are the most important.

[Improved coronary vasodilator capacity by drug lipid lowering therapy in patients in the early stage of coronary atherosclerosis with reduced coronary reserves and moderate LDL hypercholesteremia]. / Verbesserung der koronaren Vasodilatationskapazität durch medikamentöse Lipidsenkung bei Patienten im Frühstadium der koronaren Atherosklerose mit eingeschränkter Koronarreserve und mässiggradiger LDL-Hypercholesterinämie.

BACKGROUND: An abnormal coronary flow reserve represents an early marker of impaired blood flow regulation in the natural history of coronary atherosclerosis under the impact of risk factors such as hypercholesterolemia. Our clinical investigation was aimed at assessing noninvasively the integrative coronary flow response to dipyridamole stress in 18 consecutive patients with microvascular angina, only moderately elevated LDL-cholesterol levels (168 +/- 33 mg/dl), and reduced vasodilator capacity despite normal (n = 9) or slightly abnormal (n = 9) coronary arteriograms (minimal disease with luminal irregularities and/or diameter reduction < or = 30%) before and after 6-month lipid-lowering therapy (simvastatin). METHODS: Regional and averaged myocardial blood flow were measured at rest and after dipyridamole induced vasodilation (0.56 mg/kg) using dynamic positron emission tomography (PET) and N-13 ammonia as flow tracer related to a 3-compartment kinetic model. Baseline data (mean +/- SD): 13 males, 5 females; mean age: 56 +/- 8 years; basal coronary flow: 90 +/- 22 ml/min x 100 g; after lipid intervention: 93 +/- 18 ml/min x 100 g (n.s.). Total cholesterol: 246 +/- 45 mg/dl. RESULTS AFTER 6-MONTH LIPID INTERVENTION: Total cholesterol decreased to 170 +/- 36 mg/dl (p < 0.001); mean LDL level: 97 +/- 26 mg/dl (p < 0.001). Coronary dilator capacity increased, assessed in terms of minimal coronary resistance: 0.38 +/- 0.08 vs 0.49 +/- 0.09 units at baseline (p < 0.01), myocardial blood flow under dipyridamole: 232 +/- 43 vs 186 +/- 37 ml/min x 100 g at baseline (p < 0.01), and instantaneous flow ratio: 2.6 +/- 0.7 vs 2.2 +/- 0.6 (p = 0.06). Concomitantly, a considerable regression of angina was noticed in the majority of patients. CONCLUSIONS: An improvement of the non-invasively determined integrative dipyridamole induced coronary vasodilator capacity may be achieved after 6 months by intensive lipid lowering at a very early stage of coronary atherosclerosis. Consequently, aggressive cholesterol-lowering therapy represents an antiischemic and antianginal approach suggesting, at least in part, functional reversal and probably prevention of further disease progression.

Improvement of coronary vasodilatation capacity through single LDL apheresis.

A concomitant phenomenon of hypercholesterolemia is reduced coronary vasodilatation capacity due to disturbed endothelial function. Endothelial function can be partially or completely normalized by reducing cholesterol levels through drug therapy, but it is still unclear how rapidly this desired effect is achieved. An interval of between weeks and months has been presumed. LDL apheresis (LDL-A) is capable of achieving a high-degree LDL cholesterol reduction within hours. With positron emission tomography (PET), carried out immediately before and after LDL-A, changes in coronary reserve due to this abrupt LDL cholesterol reduction could be measured both quantitatively and non-invasively. In nine patients (six women, three men) with documented coronary artery disease and hypercholesterolemia, PET was carried out immediately before and 18-20 h after LDL-A. A reduction in LDL cholesterol (from 194 +/- 38 to 81 +/- 20 mg/dl), facilitated significant improvement in myocardial blood flow (MBF) (173 +/- 63 versus 226 +/- 79 ml/min per 100 g) after pharmacologic recruitment of coronary flow capacity (dipyridamole stress), coronary flow reserve (CFR) (1.91 +/- 0.68 versus 2.48 +/- 0.68) and minimum coronary resistance (MCR) (0.61 +/- 0.18 versus 0.43 +/- 0.16 mmHg/100 g per min per ml) within 24 h. Plasma viscosity was reduced slightly, by 6.6%. Probably for the first time, a 30% improvement in coronary vasodilatation capacity could be demonstrated quantitatively and non-invasively by PET after a single LDL-A within 24 h.

Results of heart transplantation in patients with preexisting malignancies.

Twenty patients with end-stage heart failure and preexisting malignancies underwent heart transplantation at a single center, with a neoplasm-free interval before the procedure of 0 to 240 months. Twelve patients were long-term survivors (2 to 72 months); there were 2 early and 6 late deaths, thus justifying heart transplantation in patients with preexisting malignancies in individual cases.

Pathomorphological characteristics of resected mitral valves after unsuccessful valvuloplasty.

OBJECTIVE: Percutaneous mitral valvuloplasty has been shown to be an acceptable alternative to surgery as treatment for selected patients with severe mitral stenosis. We examined hemodynamic, echocardiographic, and pathomorphologic findings in a series of 308 patients undergoing balloon valvuloplasty, 41 of whom underwent subsequent surgery, in search of possible predictors of an unsuccessful outcome. INTERVENTION AND RESULTS: Patients with severe mitral stenosis underwent Inoue single ballon valvuloplasty over a 48-month period and had follow-up for a mean of 14.5+/-16.8 months (range 1 to 64 months). Of the 308 patients, 267 (Group I) were clinically improved and stable throughout follow-up, while subsequent surgery was required in 41 (Group II) after 38.2+/-143.5 days (range 1 to 1212). Significant differences between the groups were observed for NYHA class (2.7+/-0.6 vs 2.9+/-0.6, p<0.05), mitral valve area (1.0+/-0.3 vs 0.9+/-0.2 cm2, p<0.01) and left atrial endsystolic dimension by echo (51.3+/-8.0 vs 55.4+/-10.2 mm, p<0.01). Two of the 41 Group II patients underwent surgery for left to right shunting, 1 for tamponade and 2 were lost to follow-up. The excised mitral valves of the remaining 36 patients all showed calcification and/or fibrosis: 9 homogenous, 5 non-homogenous; 19 were classified as having a funnel-shaped deformity, and 3 did not fit into a discrete category. Among the funnel-shaped valves, 13 had a tear versus 6 where dilation was primarily accomplished by stretching. Only one of 9 valves with homogenous calcification was torn, whereas a tear was noted in 3 of the 5 with non-homogenous calcification. CONCLUSION: Funnel-shaped valves and those with non-homogenous distribution of calcification and/or fibrosis appear to be least suitable for balloon valvuloplasty.

Predictors of unsuccessful outcome after percutaneous mitral valvulotomy including a new echocardiographic scoring system.

BACKGROUND AND AIMS OF THE STUDY: Percutaneous mitral valvulotomy has been shown to be an accept able alternative to surgery as treatment for selected patients with severe mitral stenosis. Uncertainty still exists regarding predictors of unsuccessful outcome. MATERIALS AND METHODS: 308 patients with severe mitral stenosis underwent Inoue single balloon valvulotomy over a 48-month period and were followed up for a mean of 14.5 +/- 16.8 months (range one to 64 months). Two hundred and sixty-seven (Group I) improved clinically and remained stable throughout the follow up, while subsequent surgery was required in 41 (Group II) after 38.2 +/- 143.5 days (range one to 1,212). Clinical and echocardiographic parameters of the two groups were compared to find significant predictors of an unsuccessful outcome. RESULTS: Significant differences between the groups were observed for NYHA class (2.7 +/- 0.6 vs. 2.9 +/- 0.6, p < 0.05), mitral valve area (1.0 +/- 0.3 vs. 0.9 +/- 0.2 cm2, p < 0.01), left atrial end-systolic dimension by echo (51.3 +/- 8.0 vs. 55.4 +/- 10.2 mm, p < 0.01) and an echocardiographic scoring system including grading for eccentricity of the mitral orifice and distribution of commissural calcification (7.5 +/- 2.0 for Group I and 8.7 +/- 2.0 for Group II, p < 0.001). CONCLUSIONS: Mitral valves that are more likely to have an unsuccessful outcome can be identified by hemodynamic, clinical and echocardiographic criteria, including grading for eccentricity of the mitral orifice and distribution of commissural calcification.

Ultrasound examination of stenotic mitral valves: an in vitro study.

To determine the feasibility of currently used, intravascular ultrasound catheters (12.5 and 20 MHz, 6F and 9F, Boston Scientific Corp., Watertown, MA) for mitral valve disease, ten excised mitral valves from patients with severe mitral stenosis were examined. The specimens were fixed in a glass cylinder perfused with water. The valves were planimetered with the intravascular ultrasound system and investigated regarding pathomorphological changes. The depth field of penetration was between 1.5 and 2 cm (3 to 4 cm diameter) in the 20 MHz catheter and between 2 and 2.5 cm (4 to 5 cm diameter) in the 12.5 MHz catheter. A good correlation of the experimentally recorded valve areas could be ascertained with the Gorlin formula (r = .71, P < .05), the Doppler echocardiography method (r = .69, time method (r = .75, p < .05), and with the two-dimensional echocardiography method (r = .69, P < .05). These results show a sufficient feasibility of the currently used, intravascular ultrasound catheters and enable further steps to be taken with regard to evaluating mitral valve morphology in vivo.

[Clinical significance of the cardiovascular risk factor fibrinogen in secondary prevention]. / Klinische Bedeutung des kardiovaskulären Risikofaktors Fibrinogen in der Sekundärprävention.

Seven prospective, epidemiological studies indicate plasma fibrinogen levels (over 300-350 mg/dl) as an important, independent cardiovascular risk factor for subsequent myocardial infarction and stroke. Furthermore, several clinical studies revealed an association between fibrinogen and both the angiographic and clinical degree of coronary heart disease. In addition, a significant relation of fibrinogen with the number of occluded coronary vessels was found. The following pathophysiologic mechanism are of particular importance: Fibrinogen is a main determinant of plasma viscosity and red cell aggregation. Both phenomena deteriorate blood fluidity especially in the microcirculation. Fibrinogen plays a central role in platelet aggregation and performs an essential substrate in the coagulation cascade. Thus, high fibrinogen levels may favor a hypercoagulable state resulting in final thrombotic events of cardiovascular disease. Fibrinogen is also involved in atherogenesis by stimulating proliferation and migration of smooth muscle cells. Several determinants of fibrinogen levels are known. Smoking is the strongest one in healthy persons. This clinically important effect is dose related. Consequently, cessation of smoking is a major step to lower fibrinogen and subsequently the individual cardiovascular risk. Reduction of overweight and maintenance of regular physical activity are further nonpharmacologic means. Fibrates decrease fibrinogen about 10-30% on an average. Finally, intermittent low-dose Urokinase for end-stages of coronary artery disease and LDL-apheresis (HELP) represent additional approaches to reduce fibrinogen.

[Villous rectal adenomas and secretory diarrhea]. / Villöse Rektumadenome und sekretorische Diarrhoe.

Hypersecretion following villous adenomatosis of the rectum is demonstrated by two single case studies. Both patients exhibited a secretory diarrhea with a 2.000-2.500 and 1.000 ml daily stool volume respectively, resulting in severe and life-threatening (first patient) loss of water and electrolytes. With increasing stool volume, rising concentrations of Na and Cl were observed in the stool and approached plasma levels. Consecutively the potassium concentration decreased to values between 15 and 23.4 mmol/l in the first severe case and to 28 and 31 mmol/l in the patient with the lowest stool volume. Elevated PG-E2 concentrations in the fluid moiety of the stool (up to 13.3 ng/ml and 0.98 ng/ml respectively) as well as the response to treatment with Indomethacin support the idea of a PG-E2 induced pathological loss of water and electrolytes. While 100 mg Indomethacin/day led to cessation of symptoms in the less severe case, even 400 mg Indomethacin/day were not able to reduce the massive rectal water loss in the first most severe patient to less than 1,000 ml/day. Surgical removal of villous adenoma showing hypersecretory activity is the only promising therapy. In case of inoperability, denial of surgical intervention or just for palliative treatment prior to surgery we recommend the inhibition of PG-synthesis with Indomethacin.

[Fibrinogen and leukocyte number in coronary heart disease. Correlation with angiography and clinical degree]. / Fibrinogen und Leukozytenzahl bei koronarer Herzkrankheit. Korrelationen zum angiographischen und klinischen Schweregrad.

In 302 consecutively patients fibrinogen (Clauss method) and leucocyte count were related to the angiographic and clinical degree of coronary atherosclerosis. Fibrinogen (mg/dl) was statistically higher compared to control (C, 267 +/- 55) in patients with one-vessel disease (1-vd (306 +/- 67), 2-vd (331 +/- 73), and 3-vd (328 +/- 62)). Patients with coronary sclerosis (Scl, luminal irregularities and/or stenosis under 50%) showed a tendency to higher fibrinogen levels (291 +/- 58) as compared to controls. Leucocyte count (10(9)/L) compared to C (6.7 +/- 1.8) was significantly higher in 1-vd (7.6 +/- 2.0) and 2-vd (7.6 +/- 1.9). A subgroup analysis was performed with 100 patients having severe forms of angina pectoris (AP III according to the CCS classification, unstable angina). Hundred-sixteen patients with unstable angina (390 +/- 79), particularly with angina at rest during the last 48 h were characterized by the highest fibrinogen values (423 +/- 89, class III B/C Braunwald). Leucocyte count in patients with stable angina (7.2 +/- 1.4) and angina at rest (9.3 +/- 2.7) was significantly higher as compared to control (6.7 +/- 1.8). Hyperfibrinogenemia and relative leucocytosis correlate with the angiographic and clinical extent of coronary artery disease and may offer evidence of a higher degree of thrombogenesis associated with components of inflammation.

[Histamine effects on the heart with special reference to cardiac side effects of H2 receptor antagonists]. / Histaminwirkungen am Herzen unter besonderer Berücksichtigung kardialer Nebenwirkungen von H2-Rezeptor-Antagonisten.

The existence of cardiac h1- and h2-receptors is evidenced by pharmacologic studies. Despite of the relatively high content of cardiac histamine it is not clarified whether histamine actually plays a physiologic role - apart from pharmacologic effects - in the regulation of myocardial function and coronary blood flow. Under pathophysiologic conditions (during anaphylaxis, surgical procedures, accidents, stress etc.), however, when a local or systemic histamine release occurs both hemodynamic and arrhythmogenic effects are evident. Numerous studies in animal models conclusively demonstrated a role of cardiac histamine as a major mediator of serious arrhythmias. Consequently, a combination of h1- and h2-receptor antagonists (f.e. Dimetinden/Cimetidin) was recommended as a prophylactic treatment against severe anaphylaxis including life-threatening arrhythmias for cardiac patients at risk. There is pharmacologic evidence of both a positive inotropic and chronotropic effect in the human heart via h2-receptor and stimulation of adenylate cyclase. Histamine-induced coronary effects such as vasoconstriction via h1-receptor and coronary dilatation via h2-receptor are not yet sufficiently validated. Studies on the human heart in vitro using coronary strips from explanted hearts and in vivo investigations on the intact coronary system yielded conflicting results. H2-receptor blocking agents cimetidine, ranitidine and famotidine have qualitatively a different pharmocodynamic spectrum of side effects due to differences in chemical structure. Data on cardiac arrhythmias are mostly associated to cimetidine. Symptomatic bradycardia were reported for both ranitidine and cimetidine. A possible negative inotropic effect of famotidine, although presently not validated, requires further studies. Causative and adverse side effects of cimetidine on the cardiovascular system, however, are to be expected extremely seldom due to easily reversible competetive h2-receptor binding. For prophylaxis rapid intravenous injections of h2-blockers, particularly in elder patients with cardiac diseases, should be avoided. Compared to cimetidine, a tendency of explainable difference seems to become apparent for ranitidine and famotidine due to higher receptor affinity.

Comparison of the effects of right atrial, right ventricular apex and atrioventricular sequential pacing on myocardial oxygen consumption and cardiac efficiency: a laboratory investigation.

As the impact of cardiac pacing on myocardial energetics has not yet been established, this laboratory investigation was undertaken to evaluate the effects of right atrial (AP), right ventricular apex (VP) and atrioventricular sequential pacing (AVP) on cardiac energetics in a closed-chest model. Ninety-two pacing interventions were performed in ten anesthetized mongrel dogs with normal loading conditions and contractile states. The energetic effects of pacing were assessed in terms of myocardial oxygen consumption (MVO2), its hemodynamic determinants and cardiac efficiency. Efficiency was calculated as the ratio of O2-equivalent of external cardiac work to MVO2, using standard definitions. In the first series of experiments 36 intra-individual comparisons were made between AP and VP at identical rates (95-210 beats/min). In the second series AVP was compared to VP in 10 intra-individual comparisons at identical rates (109-190 beats/min). MVO2 was lower (p less than 0.001) during AP (8.30 +/- 2.14 ml O2/min.100 g) compared to VP (10.16 +/- 3.15 ml O2/min.100 g) at the same rate (158 +/- 32 beats/min). Efficiency (p less than 0.001) was considerably higher during AP (21.6 +/- 5.7%) compared to VP (12.8 +/- 5.9%). During AVP, MVO2 (10.85 +/- 1.76 ml O2/min.100 g) was not significantly different from VP (10.57 +/- 1.34 ml O2/min.100 g) at the same rate (146 +/- 25 beats/min). Hemodynamics were superior with AVP compared to VP. Efficiency was significantly higher (p less than 0.01) with sequential (15.4 +/- 3.9%) as compared to ventricular pacing (12.0 +/- 3.2%). In conclusion, this study indicated that VP exerts disadvantageous effects on MVO2 and cardiac efficiency. AP has beneficial effects on cardiac energetics because it improves the relationship between mechanical performance of the heart and its energy requirements. AVP results in a higher efficiency than VP due to superior hemodynamics, despite MVO2 levels comparable to those of VP. The mechanism of energy waste with right ventricular apex pacing is probably related to an asynchronous contraction in the ventricular myocardium due to a nonphysiological spread of excitation.

The effect of ion composition on cellular membrane potentials during selective coronary arteriography.

An animal experimental study on seven thoracotomized dogs was designed to investigate the effects of intracoronarily injected sodium meglumine diatrizoate on myocardial electrophysiology and to evaluate the contribution of the corresponding changes of electrolyte levels in coronary blood. For this purpose the effects of alterations in the Na+-, K+- and Ca++-concentrations in coronary blood were studied separately by intracoronarily injected model solutions. Membrane potentials were recorded from the left ventricular myocardium by a modified microelectrode technique which is applicable to the beating and blood perfused heart in situ. Following selective coronary arteriography there was a temporary hyperpolarization of resting potentials and a prolongation of action potentials which may be explained by a contrast-induced local deficiency of potassium and calcium ions and by a relative prevalence of sodium ions in coronary blood. In selective coronary arteriography the synchronicity of cardiac excitation is disturbed by the regional prolongation of action potentials, which may induce ventricular arrhythmias.

Increase of myocardial oxygen consumption due to active diastolic wall tension.

A marked increase in left ventricular diastolic pressure ( PLVD ) relative to volume is regularly observed during angina pectoris and may contribute to further deteriorations of myocardial perfusion in the ischemic myocardium and to pulmonary congestion as well. A possible simultaneous increase in myocardial oxygen consumption (MVO2) due to a reversible diastolic tone during transient ischemia has not been taken into consideration in previous studies on alterations in ventricular diastolic properties. 13 closed-chest experiments were carried out in clinical catheterization technique with situations of high PLVD (18-50 mm Hg) relative to volume induced by right ventricular pacing (n = 19; 172 +/- 5 beats/min) and catecholamine-induced reversible diastolic tone (n = 17) in moderate hypothermia (31 degrees C). MVO2 was directly measured and indirectly calculated from its hemodynamic determinants using Bretschneider's equation (Et) that does not consider ventricular diastolic pressure. In addition, an energy demand for maintenance of active diastolic wall tension (E5) was calculated from PLVD , mean ventricular diastolic volume estimated from endsystolic and stroke volume, diastolic time and heart rate in ml O2/min X 100 g. During pacing tachycardia with high PLVD (27.4 +/- 1.8 mm Hg) the MVO2 (12.49 +/- 0.50 ml O2/min X 100 g) exceeds Et (10.11 +/- 0.25 ml O2/min X 100 g) (p less than 0.001), partly due to neglect of E5 (1.39 +/- 0.11 ml O2/min X 100 g). During catecholamine-induced high PLVD (31.1 +/- 2.5 mm Hg) the MVO2 (12.29 +/- 0.83 ml O2/min X 100 g) increases significantly (p less than 0.001) over Et (10.43 +/- 0.81 ml O2/min X 100 g). Addition of E5 (1.76 +/- 0.14 ml O2/min X 100g) to Et abolishes the differences between MVO2 and Et yielding non-significantly different values. Results indicate by means of indirect energetic evidence the occurrence of a diastolic tone of the heart under unphysiologic conditions. Acute increases in PLVD during angina pectoris are supposed to increase MVO2 markedly due to an additional energy demand for maintenance of reversible active diastolic wall tension.