Optical transmission of normal and atheromatous arterial wall: a spectral analysis

In laser angioplasty one of the factors influencing the immediate damage (and therefore the risk of acute arterial perforation) is the optical absorption characteristics of the target tissue. In an attempt to evaluate the differences in optical absorptive properties, the transmission spectrograms of samples of normal and atheromatous human postmortem aortic wall were measured over the visible spectrum. Optical transmission varied inversely with sample thickness and directly with wavelength through both normal and atheromatous samples. Over the whole visible spectrum atheromatous tissue transmitted less per unit thickness than normal tissue. This differential effect was, however, most pronounced at 500 nm, where atheromatous tissue transmitted light 5-10 times less strongly than normal aortic wall. Such wavelength dependent differential optical absorption could provide a means for the selective photovaporisation of atheroma in laser angioplasty.     

Six minute walking test for assessing exercise capacity in chronic heart failure

Twenty six patients, mean age 58 years (range 36-68), with stable chronic heart failure, New York Heart Association class II-III, and 10 normal subjects of a similar age range were studied. Exercise capacity was assessed by determining oxygen consumption reached during a maximal treadmill exercise test and by measuring the distance each patient walked in six minutes. There were significant differences in the distance walked in six minutes between normal subjects, patients with heart failure, class II, and those with class III heart failure (683 m, 558 m, and 402 m, respectively (p less than 0.003)). The relation between maximal oxygen consumption and the distance walked in six minutes was curvilinear; thus the distance walked varied considerably in those with a low maximal oxygen consumption but varied little in patients and normal subjects with a high maximal oxygen consumption. All subjects preferred performing the six minute walking test to the treadmill exercise test, considering it to be more closely related to their daily physical activity. The six minute test is a simple objective guide to disability in patients with chronic heart failure and could be of particular value in assessing patients with severe heart failure but less useful in assessing patients with mild heart failure.     

Coronary sinus pH during percutaneous transluminal coronary angioplasty: early development of acidosis during myocardial ischaemia in man

Coronary sinus pH was measured continuously in eight patients undergoing angioplasty to the left anterior descending coronary artery. A catheter tip pH sensitive electrode with a response time of less than 300 ms and an output of greater than or equal to 57 mV/pH unit was placed high in the coronary sinus. Recordings were obtained during a total of 24 balloon occlusions of the left anterior descending coronary artery varying in duration from 5 to 45 s. Continuous 12 lead surface electrocardiograms were recorded. During or after balloon inflation of greater than or equal to 12 s (n = 4) there was no change in coronary sinus pH or the electrocardiogram. During balloon inflation of greater than or equal to 15 s (n = 20) coronary sinus pH was unaltered but between 4 and 6 s after balloon deflation coronary sinus pH fell transiently by between 0.010 and 0.120 pH units before returning to the control value within 65 s. Ischaemic changes were seen on the electrocardiogram during 15 balloon occlusions. In individual patients the peak fall in coronary sinus pH was related to the duration of occlusion of the left anterior descending coronary artery. A rise in coronary sinus pH (alkalosis) was never seen. In man acidosis occurs in the myocardium after short periods (greater than or equal to 12 s) of ischaemia. The fall of pH precedes ischaemic changes on the surface electrocardiogram and occurs concurrently with the earliest reported changes in contractile function.     

Abnormal autonomic control of the cardiovascular system in syndrome X

Anomalies of autonomic control of the coronary circulation may play a role in the development of syndrome X (angina pectoris, ischemia-appearing results on exercise test, and normal coronary arteriograms). Twenty-six patients with syndrome X and 20 healthy sex- and age-matched control subjects were studied by means of analysis of heart rate variability during 24-hour Hotter monitoring. Spectral and nonspectral parameters of heart rate variability were investigated. Mean heart rate was similar in patients with syndrome X and in control subjects. Patients with syndrome X had significantly lower standard deviation of all normal RR intervals, a lower percentage of adjacent normal RR intervals >50 ms in difference (126.4 ± 22 vs 149 ± 43 ms, p <0.05; 6.3 ± 4 vs 11.2 ± 7%, p <0.05; respectively), and a trend toward lower values of time-domain parameters. Lower values of total power and low frequency were also observed in patients with syndrome X (1273 ± 693 vs 1790 ± 989 ms², p <0.05; 406 ± 176 vs 729 ± 455 ms², p <0.01, respectively). An inverse correlation between heart rate and measures of heart rate variability was found in syndrome X but not in control subjects. High- and low-frequency power showed a similar circadian pattern in syndrome X patients and control subjects. Patients and control subjects were then allocated into 2 groups according to the median RR duration: syndrome X1 and control 1 with high mean heart rate, and syndrome X2 and control 2 with low mean heart rate. The syndrome X1 group had a significantly lower standard deviation of all normal RR intervals, root-mean-square difference of successive RR intervals, percentage of adjacent normal RR intervals >50 ms different, and high and low frequency than did the syndrome X2, control 1, and control 2 groups. In conclusion, patients with syndrome X have a sympathovagal balance shifted toward sympathetic predominance that is more evident in those with an increased mean heart rate. This dysfunction appears to persist throughout the 24 hours and may indicate heterogeneity in autonomic function in syndrome X.     

Different effects of thiopental in severe hypoxia, total ischemia, and low-flow ischemia in rat heart muscle

The effect of thiopental (100 mg X 1(-1] during total ischemia, low-flow ischemia, and severe hypoxia with maintained flow was investigated in the isolated perfused rat heart. During total ischemia the rate of decline of tissue creatine phosphate and adenosine triphosphate was no different in thiopental-treated and untreated hearts. The development of ultrastructural damage during total ischemia, the release of creatine kinase on reperfusion, and the exacerbation of ultrastructural damage after reperfusion were unaffected by thiopental. When thiopental was added to the perfusate during hypoxia and during low-flow ischemia at a normal pH(7.4), creatine kinase release during reoxygenation and during reperfusion was significantly less (P less than 0.005 and P less than 0.05, respectively) than in the untreated groups. After low-flow ischemia at a low pH (6.5), creatine kinase release was no different in thiopental-treated and untreated hearts. Thus, thiopental afforded protection of the myocardium in hypoxia and low-flow ischemia at pH 7.4 but not in total ischemia and low-flow ischemia at pH 6.5. The data are consistent with the hypothesis that during total ischemia and low-flow ischemia at pH 6.5, acidosis favors the entry of thiopental into the cell, causing inhibition of mitochondrial function and reduction of ATP production. During hypoxic perfusion and low-flow ischemia at pH 7.4, when the decrease in pH is less, the cardiodepressant effect of thiopental may offset any deleterious effect of the drug on intracellular organelles such as mitochondria.     

Failure to demonstrate myocardial ischaemia in patients with angina and normal coronary arteries. Evaluation by continuous coronary sinus pH monitoring and lactate metabolism

Visual judgment of stenosis severity from cine-film or single-photonemission computed tomographic dipyrida-mole perfusion imageswas compared to assessment of stenosis severity as measuredwith digital quantitative coronary angiography. Thirty patientswith angiographically verified single-vessel disease underwentdipyridamole thallium stress testing within 90 days of angiography. RESULTS: A percent diameter stenosis of 50%, a percent area stenosisof 75% and a stenotic flow reserve of <3·75 measuredby quantitative coronary angiography (CMS, version 1·1,Medis Inc.) corresponded to haemodynamically significant stenosisas evaluated by visual estimates from cine-film or perfusionimages. Quantitative coronary angiography percent diameter stenosis(51·2% ± 12.6%) correlated closely (r=0·74)but underestimated significantly visual assessment of stenosisseverity from cine-film (69·3% ±21·2% p=0·0001).However, quantitative coronary angiography percent area stenosis(74·7% ± 11·7%) more closely reflectedvisual estimates from cine-film (P=0·19). Quantitativecoronary angiography stenotic flow reserve showed the highestpositive and negative predictive value regarding visual estimatesfrom cine-film (88%, 86%) or perfusion images (88% 64%) followedby percent diameter stenosis (86% 75% 86% 56%) and percent areastenosis (87% 80% 87% 60%), respectively. CONCLUSION: Evaluation of coronary lesions by quantitative coronary angiographycorresponds closely with visual estimates from cine-film andhaemodynamic significance as evaluated by dipyridamole perfusionimages. (Eur Heart J 1996; 17: 1167–1174)     

Familial restrictive cardiomyopathy with atrioventricular block and skeletal myopathy

Five generations of an Italian family with an autosomal dominant restrictive cardiomyopathy are described. Members of four generations were examined. Symptoms usually developed in the third or fourth decade but the disease did occur in childhood. Initially the condition was characterised by normal ventricular size and systolic function with increased diastolic filling pressures in both ventricles and consequent bi-atrial enlargement. Cardiac catheterisation showed a left ventricular filling pattern of "dip and plateau". The electrocardiogram typically showed non-specific changes in the ST segment and T wave and changes indicating considerable atrial enlargement, which were confirmed by echocardiography. Light microscopy of two endocardial biopsy specimens showed no specific features but excluded the endomyocardial fibrosis of eosinophilic heart disease, amyloid, and specific heart muscle diseases. At necropsy in one case examined under light microscopy extensive patchy fibrosis was found throughout the endocardium, myocardium, and subepicardium, but there were no features typical of eosinophilic heart disease. Histopathological and biochemical examination of skeletal muscle identified no abnormality. The disease often had an insidious course over five to ten years after presentation. Bundle branch blocks, leading to complete atrioventricular block, however, often occurred and may be the first manifestation. Some individuals who survived into the fifth decade developed a progressive, non-wasting skeletal myopathy.     

Extrapolated maximal oxygen consumption: a new method for the objective analysis of respiratory gas exchange during exercise

Respiratory gas exchange was measured during maximal treadmill exercise testing in six healthy volunteers and 20 patients with chronic heart failure. A curve of equation y = ax-bx2 was used to model the relation between the rate of oxygen consumption (y axis) and the rate of carbon dioxide production (x axis). The constants "a" and "b" were used to calculate the maximal value of the expression ax-bx2. This value was termed the "extrapolated maximal oxygen consumption". For all subjects a close fit between experimental data and mathematical model was obtained and the values of the measured maximal rate of oxygen consumption and "extrapolated maximal oxygen consumption" were similar. Respiratory gas exchange was reanalysed using only those values obtained during the first 90%, 75%, and 66% of exercise. In contrast with the value for the measured rate of oxygen consumption, the value of "extrapolated maximal oxygen consumption" was effectively independent of exercise duration. Extrapolated maximal oxygen consumption provides an objective measure of cardiorespiratory functional reserve that, within limits, is independent of exercise duration. Extrapolated maximal oxygen consumption is complementary to the direct measurement of the maximal rate of oxygen consumption and increases the amount of information derived from a single exercise test.     

Stress (Takotsubo) cardiomyopathy--a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning

Stress cardiomyopathy, also referred to as Takotsubo cardiomyopathy, is an increasingly recognized clinical syndrome characterized by acute reversible apical ventricular dysfunction. We hypothesize that stress cardiomyopathy is a form of myocardial stunning, but with different cellular mechanisms to those seen during transient episodes of ischemia secondary to coronary stenoses. In this syndrome, we believe that high levels of circulating epinephrine trigger a switch in intracellular signal trafficking in ventricular cardiomyocytes, from G(s) protein to G(i) protein signaling via the beta(2)-adrenoceptor. Although this switch to beta(2)-adrenoceptor-G(i) protein signaling protects against the proapoptotic effects of intense activation of beta(1)-adrenoceptors, it is also negatively inotropic. This effect is greatest at the apical myocardium, in which the beta-adrenoceptor density is greatest. Our hypothesis has implications for the use of drugs or devices in the treatment of patients with stress cardiomyopathy.