Sea-floor hydrothermal activity links climate to tectonics: the Eocene carbon dioxide greenhouse.

Two important findings of recent ocean floor drilling in the southeast Pacific (Deep Sea Drilling Project Leg 92) are (i) that sea-floor hydrothermal activity may fluctuate through time by as much as an order of magnitude and (ii) that episodes of greatest hydrothermal flux correspond to times when ridge-transform plate boundaries are undergoing major changes in their configuration rather than to known times of increased spreading rate or volcanism. Evidence is presented here in support of the hypothesis that heightened hydrothermal activity induced by the Eocene tectonic activity caused a global greenhouse effect, which may represent the long-sought-after historical analog to the carbon dioxide-induced global warming expected to occur by the middle of the next century.

Depression of systolic and diastolic myocardial reserve during atrial pacing tachycardia in patients with dilated cardiomyopathy.

Previous reports have shown that increases in heart rate may result in enhanced left ventricular (LV) systolic and diastolic performance. To assess whether this phenomenon occurs in the presence of depressed LV function, the effects of pacing on LV pressure and volume were compared in seven patients with dilated cardiomyopathy (LV ejection fraction 0.19 +/- 0.11) and six patients with no or minimal coronary artery disease (LV ejection fraction 0.69 +/- 0.11). Patients with normal LV function demonstrated significant increases in LV peak-positive dP/dt, LV end-systolic pressure-volume ratio, LV peak filling rate, and a progressive leftward and downward shift of their pressure-volume diagrams, compatible with increased contractility and distensibility in response to pacing tachycardia. There was no change in LV peak-negative dP/dt or tau. Patients with dilated cardiomyopathy, in contrast, demonstrated no increase in either LV peak-positive dP/dt or the end-systolic pressure-volume ratio, and absence of a progressive leftward shift of their pressure-volume diagrams. Moreover, cardiomyopathy patients demonstrated no increase in LV peak-negative dP/dt or LV peak filling rate and a blunted downward shift of the diastolic limb of their pressure-volume diagrams. Tau, as determined from a derivative method, became abbreviated although never reaching control values. We conclude that patients with dilated cardiomyopathy may demonstrate little or no significant enhancement in systolic and diastolic function during atrial pacing tachycardia, suggesting a depression of both inotropic and lusitropic reserve.

Influence of contrast media on thrombus formation during coronary angioplasty.

The influence of contrast media on thrombus formation during percutaneous transluminal coronary angioplasty was assessed in 124 consecutive patients undergoing coronary angioplasty and receiving either ionic (n = 57) (Group I) or nonionic (n = 67) (Group II) contrast medium. The presence of thrombus was assessed by qualitative analysis of angiograms in identical pre- and postangioplasty projections by four observers who had no knowledge of other data. Quantitation of stenosis severity before and after angioplasty and qualitative analysis of lesion eccentricity and complexity and of the presence of dissection were also performed. Although the baseline clinical characteristics of the two groups (including presenting syndromes and procedural and angiographic variables) did not differ, more patients in Group II than Group I developed new thrombus during coronary angioplasty (18% vs. 4%, p less than 0.02). In particular, patients with a presenting syndrome of recent myocardial infarction or rest angina, or both, and patients with an eccentric coronary plaque were more likely to develop new thrombus if they received nonionic than if they received ionic contrast medium (p less than 0.05). Patients with new thrombus formation and patients with thrombus present both before and after angioplasty had a high incidence of acute procedural complications (36% and 23%, respectively). Patients in Groups I and II had a similar incidence of ischemic events during follow-up.

Postprandial lipemia: the origin of an early peak studied by specific dietary fatty acid intake during sequential meals.

Previous studies have noted the presence of an early postprandial peak in plasma triacylglycerol concentration, particularly when successive meals have been consumed. We tested the hypothesis that fat from a previous meal contributes to this early postprandial lipemia. We investigated the effect of consuming a lunch containing 61 g fat 5 h after a breakfast containing 54 g fat. The predominant fatty acids in the first meal, expressed as % by wt of total fatty acids, were 18:2 (linoleic acid), 68%, and 18:1 (oleic acid), 19%. The main fatty acids in the second meal were 18:1 (75%) and 18:2 (8%). After lunch, the early peak (at 50-60 min) in chylomicron triacylglycerol was found to contain a large proportion of 18:2, the main constituent of the first meal, whereas at later time points the chylomicron triacylglycerol fatty acid profile more closely resembled that of the second meal. Control studies in three subjects showed the complete absence of the early peaks in plasma and chylomicron triacylglycerol concentrations when either the lunch was omitted or the first meal was low in fat. The plasma nonesterified fatty acid profile also showed a corresponding peak in 18:2 at 50-60 min, which may represent the release into the plasma of fatty acids arising from the hydrolysis of chylomicron triacylglycerol by adipose tissue lipoprotein lipase.

Influence of left ventricular mass on coronary artery cross-sectional area.

Observations from cardiac catheterization suggest that coronary artery cross-sectional area (CSA) is increased in patients with left ventricular (LV) hypertrophy and is proportional to LV mass. This hypothesis was tested using computer-based quantitative analysis of LV mass and CSA from angiographic images of the left ventricle and proximal coronary arteries from 19 men and 21 women, aged 23 to 78 years (mean 56). Twenty-seven patients had valvular heart disease, 16 of whom had multivalvular involvement; diagnoses included aortic stenosis in 19, aortic regurgitation in 13 and mitral regurgitation in 12. Thirteen patients had normal valvular and ventricular function. All patients had normal coronary arteries. Significant differences between normal patients and those with valvular disease were noted in LV mass (88 +/- 7 vs 165 +/- 12 g/m2, p less than 0.001) and coronary CSA (26 +/- 2 vs 46 +/- 3 mm2, p less than 0.001). Furthermore, a linear relation between LV mass and coronary CSA was noted (r = 0.788, p less than 0.001). Thus, proximal coronary artery CSA is significantly larger in valvular heart disease patients with LV hypertrophy than in those with normal ventricles, and proximal coronary artery area increases in proportion to LV mass in hypertrophied ventricles.

Comparison of monoplane and biplane assessment of regional left ventricular wall motion after thrombolytic therapy for acute myocardial infarction.

Regional left ventricular (LV) function was assessed using serial biplane orthogonal LV angiograms recorded before and after reperfusion therapy for acute myocardial infarction (AMI) in 24 patients. Improvement in regional LV function was seen in only 5 patients after reperfusion therapy when only the right anterior oblique view was analyzed; improvement in regional wall motion was seen in 14 when biplane views were analyzed. Biplane analysis was particularly important in the 12 patients with right coronary artery occlusion, among whom the right anterior oblique view showed improvement in only 1 patient but the left anterior oblique view showed improvement in 6 patients (p less than 0.05). Biplane analysis is more sensitive than monoplane right anterior oblique analysis alone for detecting improvement in LV function after reperfusion therapy for AMI. However, both views are complementary, adding information about regional function not revealed by either view alone.

Is tau a preload-independent measure of isovolumetric relaxation?

Several studies have been performed in patients with a variety of myocardial diseases that have identified a prolongation of tau. However, it is not clear whether prolongation of tau represents abnormal myocardial physiology or the effect of excessive load associated with a particular disease process. Accordingly, we evaluate the effect on tau of an isolated decrease in preload induced by inferior vena cava occlusion before the appearance of reflex changes in six patients designated as normal by catheterization criteria. A computer-based digitization routine identified cardiac contractions in all patients early after inferior vena cava occlusion where left ventricular end-diastolic pressure decreased (18.3 +/- 6.3 to 9.3 +/- 5.8, p less than 0.05) while left ventricular systolic pressure (113.3 +/- 13.8 to 111.8 +/- 14.0, p = NS) and heart rate (66.0 +/- 10.0 to 65.9 +/- 10.3, p = NS) did not change. After this alteration in preload, no change in tau from baseline, as calculated by the logarithmic (TL), derivative (TD), or method of Mirsky (T1/2), was noted: TL, 47.4 +/- 6.5 to 44.6 +/- 7.6; TD, 39.3 +/- 8.1 to 39.8 +/- 8.4; T1/2, 33.0 +/- 4.0 to 31.8 +/- 4.6; all p = NS. The baseline pressure extrapolated from isovolumetric relaxation did not change in these preload beats compared with baseline (+4.26 +/- 6.20 to -0.80 +/- 4.87, p = NS). Subsequent beats were identified where left ventricular systolic pressure showed a numeric decrease compared with baseline (113.3 +/- 13.8 to 100.8 +/- 14.3, p = NS) despite no change in heart rate (66.0 +/- 10.0 to 66.8 +/- 10.5, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Effectiveness of recombinant desulphatohirudin in reducing restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits.

BACKGROUND: The effectiveness of balloon angioplasty is limited by a restenosis rate of approximately 30%. Recombinant desulphatohirudin (r-hirudin [CGP 39393]) has been found to be highly effective in preventing acute platelet-rich thrombosis after deep arterial injury as compared with heparin. METHODS AND RESULTS: This study evaluated the effect of intravenous r-hirudin, a selective inhibitor of thrombin, on restenosis after balloon angioplasty in 29 rabbits. Focal femoral atherosclerosis was induced by air desiccation endothelial injury followed by a 2% cholesterol diet for 1 month. At angioplasty (2.5-mm balloon with three 60-second, 10-atm inflations 60 seconds apart), the rabbits received heparin (150 units/kg bolus, n = 16) or r-hirudin (1 mg/kg bolus followed by infusions of 1 mg/kg for the first hour and 0.5 mg/kg for the second hour, n = 13). Angiograms performed before and after angioplasty and before death were analyzed quantitatively by a blinded observer. Rabbits were killed 2 hours (n = 14) or 28 days (n = 15) after angioplasty. Femoral arteries were fixed in situ by perfusion of 10% formaldehyde at 100 mm Hg. The mean luminal diameter of the arteries with successful angioplasty (greater than or equal to 20% increase in luminal diameter) in rabbits treated with heparin (n = 8 arteries) increased from 1.18 +/- 0.29 mm before angioplasty to 1.86 +/- 0.24 mm immediately after angioplasty (p less than 0.001) and decreased to 0.94 +/- 0.69 mm (p = 0.0004) at 28 days after angioplasty. In rabbits treated with r-hirudin (n = 11 arteries), the mean luminal diameter increased from 1.14 +/- 0.17 mm before angioplasty to 1.68 +/- 0.20 mm immediately after angioplasty (p less than 0.001) and decreased to 1.37 +/- 0.47 mm (p = 0.01) at 28 days after angioplasty. The mean reduction in luminal diameter by angiography was less in the r-hirudin-treated group than in the heparin-treated group (0.30 +/- 0.33 versus 0.92 +/- 0.61 mm, p = 0.01). Blinded planimetric analysis of stained histological sections of the femoral arteries also showed less cross-sectional area narrowing by plaque in rabbits treated with r-hirudin compared with those treated with heparin (22 +/- 16% verus 48 +/- 29%, p = 0.01). Both groups had similar numbers of arteries with histological evidence of balloon-induced plaque tear (12 of 13 versus 13 of 15). CONCLUSIONS: Rabbits receiving r-hirudin at the time of experimental balloon angioplasty had significantly less restenosis by angiography and by quantitative histopathology than rabbits receiving heparin.

Demonstration of an imbalance between coronary perfusion and excessive load as a mechanism of ischemia during stress in patients with aortic stenosis.

Patients with aortic stenosis are susceptible to myocardial ischemia during hemodynamic stress, which may be caused by two mechanisms. First, vascular abnormalities inherent in myocardial hypertrophy may impair coronary vasodilation, limiting the ability to increase coronary blood flow to meet increased metabolic demands. Second, aortic stenosis itself may cause an imbalance between oxygen supply and demand during hemodynamic stress by decreasing aortic pressure (decreasing coronary perfusion or oxygen supply) and increasing left ventricular pressure (increasing oxygen demand). By decreasing aortic valve gradient without immediately altering ventricular hypertrophy, aortic balloon valvuloplasty offers the opportunity to distinguish these mechanisms. We hypothesized that aortic valvuloplasty would improve the balance between myocardial oxygen supply and demand, especially during isoproterenol infusion. Nine patients undergoing aortic balloon valvuloplasty were assessed at baseline and during isoproterenol infusion (5 +/- 2 micrograms/min, mean +/- SD) before and after valvuloplasty. Valvuloplasty increased myocardial oxygen supply. After valvuloplasty, isoproterenol decreased diastolic pressure time index (DPTI) less and increased coronary sinus blood flow more than before valvuloplasty (-630 +/- 367 vs. -292 +/- 224 mm Hg.sec/min, p = 0.02 and 53 +/- 137 vs. 179 +/- 145 ml/min, p = 0.001, respectively). Valvuloplasty also decreased oxygen demand, decreasing systolic pressure time index (SPTI) from 4,135 +/- 511 to 3,021 +/- 492 mm Hg.sec/min (p = 0.0002). Valvuloplasty improved the balance between myocardial oxygen supply and demand, increasing baseline DPTI:SPTI, decreasing aortocoronary sinus oxygen content difference (0.51 +/- 0.15 to 0.68 +/- 0.14, p = 0.005 and 96 +/- 14 to 78 +/- 15 ml O2/l, p = 0.002, respectively), and decreasing myocardial lactate production during isoproterenol infusion (mean lactate extraction fraction, -0.26 +/- 0.40 to 0.14 +/- 0.17; p = 0.01). We conclude that aortic valvuloplasty improves the balance between myocardial oxygen supply and demand during hemodynamic stress induced by isoproterenol infusion. We speculate that the clinical improvement, which often occurs in these patients after valvuloplasty despite persistence of hemodynamically "critical" aortic stenosis, is in part attributable to immediate improvement in the myocardial oxygen supply:demand ratio.

Estimation of the effects of angioplasty on coronary stenosis using quantitative video angiography.

In this study, we compared stenosis severity by quantitative coronary angiography from video and cine images with visual estimation in 14 patients who underwent PTCA. Both cine and video analysis demonstrated a change from 65.2 +/- 2.5 to 36.5 +/- 3.1% diameter stenosis following PTCA, whereas visual estimation (average of three observers) showed improvement from 89.9 +/- 1.7 to 36.0 +/- 3.2%. Percent area stenosis from quantitative angiography showed improvement from 87.9 +/- 1.8 to 56.4 +/- 5.8. These data indicate that visual assessment overestimated percent diameter of severe lesions. To determine if video analysis could provide rapid quantitative assessment of PTCA results, we compared percent diameter and percent area stenosis by video with cine (diameter: correlation coefficient, 0.82; slope, 0.79; area: correlation coefficient, 0.86; slope, 0.83). These results indicate that video-based measurements are not different from cine-derived measurements. Quantitative coronary angiography provides an accurate estimate of changes produced by PTCA and can be performed rapidly and accurately on video images, thus making results available during the PTCA procedure.

Reactions to tetanus toxoid.

In a factory population the occurrence of reactions to tetanus toxoid was recorded after 6740 injections. The incidence of general reactions was 0.3% and of local reactions 2.6%. The local reaction rate to the first injection of the basic immunization course was 0.9%, to the second injection 2.7%, and to the third injection 7.4%. To booster injections the rate was 1.6%. The local reaction rate was appreciably higher in women than in men - 14.4% and 5.7% respectively in the case of the third injection - and the incidence among women increased with age.Tetanus vaccine containing 10 Lf of toxoid caused fewer reactions than one containing 20 Lf, but a reduction in the content of aluminium adjuvant did not affect the reaction rate.Almost all reactors were found to have a satisfactory serum antitoxin concentration at the time of the reaction or developed a satisfactory immunity within 1-6 months.Skin tests were made in 32 hypersensitive patients. Neither the diluent, thiomersal preservative, nor the culture medium appeared to be responsible for hypersensitivity. The degree of hypersensitivity elicited by a special highly purified toxoid was only very slightly less than that elicited by the commercially pure toxoid. It is suggested that reactions are largely due to the toxoid antigen itself rather than to impurities or other components of the vaccine.