Biomedical subjects
Publications and source records attributed to D T Kelly.
Indians have highest incidence of coronary heart disease. Here it occurs much more prematurely. Endothelial dysfunction has been increasingly recognised as an early event for the development of various cardiovascular disease. Long acting nifedipine has a definite role to play in reversing endothelial dysfunction.
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The factors which have led to a dramatic increase in the numbers of the elderly and the impact of this ageing population on health care resources is discussed. The importance of looking at the total disease burden of a particular disorder rather than just its mortality rate is emphasized, particularly in regard to cardiovascular disease.
The cumulative evidence acquired over 20 years suggests that beta-blockers improve functional capacity, ventricular function, and decrease mortality in patients with heart failure either due to dilated cardiomyopathy or ischaemic heart disease. This effect is independent of the beneficial effects of digoxin, diuretics and particularly ACE inhibitors and has resulted in re-evaluation of requirements for transplantation in patients with advanced cardiac failure. Ninety percent of patients appear to respond to beta-blockers but no clinical or biochemical parameters can identify a favourable response. The beneficial effects occur slowly but last for years. Further ongoing trials will provide more information but beta-blockade therapy should be considered in addition to other therapy in the management of heart failure.
OBJECTIVES: This study was conducted to determine whether rebound ischemia occurs during nitrate-free periods with intermittent cutaneous nitroglycerin therapy in patients with angina pectoris who are receiving background antianginal therapy. BACKGROUND: Rebound angina has been suggested to be a complication of the nitrate-free period with long-term cutaneous nitroglycerin therapy given intermittently to prevent tolerance. METHODS: Fifty-two patients with stable effort angina taking either a beta-adrenergic blocking agent (n = 25) or diltiazem (n = 22) or their combination (n = 5) completed a randomized, double-blind, placebo-controlled crossover study of cutaneous nitroglycerin patches (50 mg). Active or placebo patches were worn for 1 week, applied at 8 AM and removed at 10 PM to provide a 10-h daily nitrate-free (or placebo-free) period. During the last 48 h of each study phase, a Holter monitor was used to detect ischemia. RESULTS: Only 31 patients experienced ischemia during either phase of the study (23 during the patch-off period). A total of 463 ischemic episodes were recorded: 246 during placebo and 217 during nitroglycerin (p = 0.8, for per patient comparison). The majority (88%) of ischemic episodes were silent. Mean (+/- SEM) duration of ischemia during the total 48-h period was similar during active and placebo phases (35.5 +/- 15.0 min/24 h for active therapy vs. 29.7 +/- 9.8 for placebo, p = 0.8). This was due to an increase in duration of ischemia with active therapy during the patch-off period (46.9 +/- 17.9 min/24 h for active therapy vs. 22.5 +/- 9.2 for placebo, p = 0.07) and a decrease during the patch-on period (27.5 +/- 14.0 min/24 h for active therapy vs. 34.5 +/- 11.0 min/24 h for placebo, p = 0.16). The pattern of diurnal distribution of ischemic episodes differed between active and placebo phases. During placebo there was a nadir in the incidence of ischemia in the overnight patch-off period, with a significantly lower incidence between midnight and 6 AM (25 episodes) compared with the mean number of episodes during the three other 6-h periods (73 episodes, p < 0.001). During the nitroglycerin patch-off period, there was a loss of this overnight nadir, with the same incidence of ischemia between midnight and 6 AM (53 episodes) as the mean number of episodes for the three other 6-h periods (54 episodes). CONCLUSIONS: The majority of patients taking background antianginal therapy experienced no ischemia during the patch-off period. In the 44% of patients with ischemia during this period, there was a nonsignificant increase in the duration of ischemia with active therapy. Although this result was statistically inconclusive, the change in the distribution of diurnal ischemia offers suggestive evidence that rebound ischemia may be a problem with regard to intermittent cutaneous nitroglycerin.
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It has previously been documented that patients with obstructive sleep apnoea (OSA) have an abnormal blood pressure (pressor) response to acute hypoxia when awake. The relationship between hypoxic chemosensitivity and 24 h blood pressure in OSA is not known. Twenty-four hour ambulatory BP (ABP) was measured at 15 min intervals for 24 h using a non-invasive device (Oxford Medilog ABP or Spacelabs 90207 recorder) in 49 men (mean age 51 +/- 9 years), with OSA. The BP response to acute hypoxia was measured either directly (radial arterial line) or indirectly (Finapress) during wakefulness. The pressor response to hypoxia (expressed as the slope of the regression line of mean BP on % fall in arterial oxygen saturation) was compared with the results of the ABP recording, sleep study data and clinical variables. A pressor response to acute hypoxia was present in all patients (mean 1.4 +/- 1.1 mmHg/% delta SaO2, range 0.1-4.5). There was a relationship between the magnitude of the pressor response to hypoxia, severity of sleep apnoea (RDI and minimum SaO2) and central obesity (waist measurement). In contrast, there was no relationship between BP response to hypoxia during wakefulness and 24-h BP. However, increasing obesity and severity of OSA were associated with loss of the normal fall in BP at night. We conclude that enhanced chemosensitivity is common in OSA but there is no demonstrable link between chemosensitivity and mean daytime or night-time ABP.
The clinical prognostic indices in unstable angina pectoris, particularly recurrent rest pain, previous angina and diabetes, plus both transient and evolutionary T wave on the ECG during the admission period and either a positive stress test at low workload or a positive Holter monitor, identify a higher risk group. By the use of these noninvasive and clinical indices it is thus possible to stratify patients with unstable angina and may help in the management of this difficult condition.
The mechanism and significance of precordial ST depression during inferior wall acute myocardial infarction (AMI) is debated. This study assessed the location and extent of arterial perfusion distribution responsible for this electrocardiographic finding. Intracoronary thallium-201 was injected in 11 patients with 1-vessel right coronary disease to delineate perfusion distribution that was quantitated by a new angiographic distribution score. The angiographic score correlated with posterior (r = 0.84), posterolateral (r = 0.88) and total (r = 0.73) extent of intracoronary thallium distribution. The angiographic distribution score was related to electrocardiographic changes in 16 patients showing an inferior ST-segment elevation during angioplasty (7 with and 9 without precordial ST depression), of which 6 received intracoronary thallium injection. None had thallium distribution in the anterior or septal segment, but there was a trend toward a greater angiographic distribution score and posterior segment thallium score in patients with precordial ST depression. In another 77 patients with inferior wall AMI due to right coronary occlusion (24 with concomitant left anterior descending narrowing), precordial ST depression was present in 16 with and 31 without left anterior descending narrowing (p = NS). The angiographic distribution score was higher in those with than without precordial ST depression (0.59 +/- 0.10 vs 0.44 +/- 0.11, p < 0.001) in both patients with and without left anterior descending disease. The magnitude of both inferior ST elevation and precordial ST depression correlated with the angiographic distribution score, but only precordial ST depression was independently related in multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
A semi-quantitative right coronary artery score (RCA score) was derived from the ratio of the number of the major left ventricular branches of the right coronary artery to the total of the right coronary and left circumflex arteries, to stratify the extent of perfusion in patients with right coronary artery dominance. Thirty-seven patients with one-vessel coronary disease involving a dominant right coronary artery proximal to the left ventricular branches were selected for study. Thallium scintigraphy was performed after right intracoronary injection in 11 patients, and 26 patients underwent conventional stress thallium scintigraphy (24 exercise thallium and two dipyridamole thallium scintigraphy). Thallium scores of perfusion region size after right intracoronary thallium injection and perfusion defect size in stress thallium studies were quantitated from planar thallium images. Both the RCA score and the regional thallium scores spanned over a wide range. The RCA score (range 0.23-0.85) correlated best with the posterior (70 degrees left anterior oblique view) plus lateral segment (40 degrees left anterior oblique view) thallium score (r = 0.88 and 0.53 for intracoronary and stress thallium studies respectively). It also correlated with the summed thallium scores in the posterior, lateral, apical and inferior segments (r = 0.73 and 0.54 respectively) but not with thallium scores in the apex or inferior segment alone. The proposed RCA score quantitates the variable posterolateral perfusion territory of the right coronary artery, and could stratify the area of myocardium at risk from coronary stenosis in the majority of patients with right coronary dominance.
Ambulatory blood pressure (BP) was measured noninvasively (Oxford Medilog ABP) at 15-minute intervals for 24 hours before and after 8 weeks of treatment with nasal continuous positive airway pressure (nCPAP) in 19 men with obstructive sleep apnea (OSA). We included both normotensive and hypertensive patients, but hypertensives were studied after withdrawal of antihypertensive drugs. Ambulatory BP before and after treatment was compared using patients as their own controls. Treatment with nCPAP was successfully established in 14 of the 19 patients (74%). Blood pressure fell significantly in patients who were successfully treated: 24-hour mean BP (systolic/diastolic) decreased from 141 +/- 18/89 +/- 11 mm Hg to 134 +/- 19/85 +/- 13 mm Hg (p < 0.05). The reduction in 24-hour mean systolic BP occurred during both day and night, but a significant fall in mean diastolic BP was only observed during the day. The mean blood pressure fell in both normotensive and hypertensive patients. Patients who were inadequately treated with nCPAP had no reduction in mean 24-hour BP. Effective treatment of sleep apnea with nCPAP was associated with a significant fall in both systolic and diastolic BP independent of changes in body weight or alcohol consumption, suggesting that sleep apnea was an independent factor contributing to elevated nighttime and daytime BP in these patients.
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Sustained oral treatment with beta blockers has been shown to improve symptoms in patients with chronic heart failure. In non-placebo-controlled trials, the administration initially of a low dose, gradually increased over a period of weeks has been demonstrated to improve both symptoms, exercise capacity and left-ventricular ejection fraction. The rationale for this treatment is the enhanced adrenergic stimulation present in heart failure which results in decreased sensitivity and density of myocardial beta-receptors. Beta blockers may decrease this pathological adrenergic drive. Carvedilol, in addition to its beta-blocking properties, is a vasodilator and is theoretically more suitable than earlier compounds of its potential to further decrease left-ventricular afterload. Recent studies have demonstrated symptomatic improvement with carvedilol in patients with heart failure, and a multicentre trial has been designed to evaluate its efficacy and safety.
Studies were conducted to determine the effect of galactan on the colonization of E. coli and lactobacilli and ileal pH and volatile fatty acid production in the digestive tract of the weanling pig. In each of two replicate trials, eight 21-d-old nursing pigs were cannulated in the terminal ileum. After a 7-d recovery period, the pigs were weaned and randomly assigned to two test diets: 1) a corn-soybean meal-based control diet and 2) a similar diet containing 1% galactan. On d 1 after weaning, all pigs were orally subjected to K88+ E. coli (2 x 10(9) colony forming units). Ileal digesta samples were collected on d 0, 2, 4, 6, 8, and 10 after weaning and assayed for total E. coli, K88+ E. coli, lactobacilli, pH, and VFA. At the end of the trials, the pigs were killed and digesta samples were collected from the stomach, duodenum, cecum, and colon. Assays similar to those performed on the digesta samples collected from ileal cannulas were performed. Pigs fed 1% galactan had lower (P < .10) ileal pH, lower (P < .05) total E. coli on d 6 and 8, and lower (P < .05) K88+ E. coli concentrations in the ileum than pigs fed the control diet. There were no differences in ADG or gain:feed ratio between diets. The VFA concentrations were not different in the ileum between diets. The VFA were higher (P < .10) on d 0 than on any other day of the study. Acetate and isobutyrate concentrations were lower (P < .10) in the cecum in pigs fed 1% galactan.(ABSTRACT TRUNCATED AT 250 WORDS)
From 2 to 4.5 months of age, 80 crossbred gilts were reared in a conventional grower unit where they were naturally exposed to mycoplasmal and bacterial pathogens that cause pneumonia and atrophic rhinitis. At 4.5 months of age, gilts were moved to environmentally regulated rooms (4.9 x 7.3 m) and assigned at random to 1 of 2 treatment groups: low aerial concentration of ammonia (4 to 12 ppm; mean, 7 ppm) or moderate aerial concentration of ammonia (26 to 45 ppm, mean, 35 ppm). Low concentration of ammonia was obtained by flushing of manure pits weekly, whereas moderate concentration of ammonia was maintained by adding anhydrous ammonia to manure pits that were not flushed. Gilts were weighed biweekly. Mean daily gain (MDG) was less (P < 0.01) for gilts exposed to moderate concentration of ammonia than for gilts exposed to low concentration of ammonia after 2 weeks in their respective environments. By 4 and 6 weeks, however, MDG was similar between the 2 treatment groups. After 6 weeks in these environments, 20 gilts from each treatment group were slaughtered, and prevalence and severity of lung lesions and snout grades were determined. At slaughter, body weight was greater (P < 0.01) in gilts exposed to low, rather than moderate, ammonia concentration (94.5 vs 86.8 kg; SEM, 3.3 kg). Percentage of lung tissue containing lesions (18 vs 12) and snout grade (2.8 vs 3.1) were similar between gilts exposed to low or moderate concentration of ammonia. The remaining 20 gilts in each treatment group were maintained in their respective environments, exposed daily to mature boars and bred at first estrus.(ABSTRACT TRUNCATED AT 250 WORDS)
The magnitude of tolerance to the anti-anginal efficacy of transdermal nitroglycerin and the efficacy and safety of short (4 h) and long (10 h) nitrate-free intervals for its prevention, were investigated in a randomized, double-blind, placebo-controlled crossover trial of 4 week-long treatment regimens: placebo, continuous therapy with a 50 mg patch (10 mg.24 h-1), and 4 h and 10 h nitrate-free periods. Only patients showing greater than 1 min increase in time to 1 mm ST depression after acute patch administration were eligible. Twelve men completed the study. One other anti-anginal medication (a beta-blocker in nine and calcium antagonist in two) was permitted in a constant dose throughout the study. Patients underwent exercise testing on days 1 and 7 of each treatment period, and 24 h ambulatory ECG monitoring on day 6. Compared to placebo, transdermal nitroglycerin on day 1 significantly improved time to 1 mm ST depression by 35%, and time to angina, exercise duration and maximal workload by 21%, 13% and 9% respectively. These improvements were totally lost after 7 days' continuous therapy, but completely maintained by a 10 h nitrate-free period (improvements of 35%, 25%, 16% and 11% respectively) but not by a 4 h nitrate-free period (non-significant improvements of 15%, 2%, 4% and 1% respectively). The differences between 10 and 4 h nitrate-free were significant for each end-point. Neither duration of ambulatory ischaemia, nor the proportion of patients experiencing greater than or equal to 5 min ischaemia during the scheduled nitrate-free interval differed between treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
AIMS: The aims of this study were to examine the circadian variation in blood pressure (BP) in obstructive sleep apnea (OSA) and to compare this between normotensive and hypertensive subjects. METHODS: We measured 24-hour ambulatory BP (ABP) in 72 men (mean age 51 +/- 8 years), with OSA diagnosed on overnight sleep study. Measurements of BP were made at 15 min intervals for 24 h using either an Oxford Medilog ABP or Spacelabs 90207 recorder. All recordings were performed after > or = 3 week washout of anti-hypertensive drugs. The day-time monitoring period was defined as 07:00 hrs to 22:00 and night-time 22:00 to 07:00. The ratio of night:day systolic and diastolic BP was calculated. RESULTS: The patients were obese (mean body mass index 33 +/- 5 kg/m2) with a central pattern of obesity (waist:hip ratio 0.99 +/- 0.14, normal < 0.94). The mean 24-h ABP (systolic/diastolic) was 138 +/- 18/88 +/- 12 mmHg. The mean daytime ABP was 143 +/- 18/93 +/- 12 and night-time ABP 128 +/- 20/80 +/- 12 Hg. The night:day BP ratio was 0.90 +/- 0.07 (systolic) and 0.87 +/- 0.09 (diastolic) indicating that average BP was lower during the night. This pattern was similar in normotensive and hypertensive subjects. In contrast there was a significant relationship between increasing BMI and night:day blood pressure ratio (r = 0.56, p < 0.001) independent of the effects of OSA. CONCLUSION: In contrast to previous studies, men with OSA have a normal diurnal pattern of blood pressure levels. These findings suggest that any influence of OSA on BP is manifested throughout the 24-h period.
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