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Biomedical subjects

A K Ellis

Publications and source records attributed to A K Ellis.

At least 19 recordsLinked to original sources
PubMed2004

Hemopneumothorax in a COPD patient treated with noninvasive positive pressure ventilation: the risk of attendant anticoagulation.

Noninvasive positive pressure ventilation (NIPPV) modalities have been proven to be effective in the setting of exacerbations of chronic obstructive pulmonary disease (COPD). Reported complications include pneumothorax, increased work of breathing, gastric distension and air embolism. This case demonstrates that patients with severe COPD on anticoagulant therapy are potentially at risk for the serious complication of combined lung barotrauma and hemorrhage while on acute NIPPV therapy. This is the first reported case of hemopneumothorax complicating NIPPV therapy.

Aged↗
PubMed2001

Quality of life indices may be predictive of placebo and medication response to treatment for allergic rhinitis.

BACKGROUND: Quality of life (QOL) is known to be an important clinical endpoint in determining medication efficacy; however, the predictive value of QOL indices for response to medication or placebo has not been tested. OBJECTIVE: To determine whether a correlation between measures of QOL and response to medication/placebo exists in an evaluation of budesonide for allergic rhinitis. METHODS: Two hundred nine participants completed the 36-item short-form health QOL survey at screening for entry into a study examining the onset of action of budesonide in an allergen challenge system. During the treatment phase, symptom assessments were recorded hourly after dosing of double-blind medication. Participants were determined to be responders or nonresponders to study medication. A responder was defined as a participant who rated medication effectiveness as fair to excellent with regard to symptom relief, for three consecutive hourly assessments during the study day or one whose total symptom score decreased by > or =25% for three consecutive hourly assessments. Baseline QOL scores were compared between responders and nonresponders. RESULTS: Differences were noted among responders and nonresponders on the basis of whether budesonide or placebo was received. Ratings of general health perception, pain, physical function, and role limitation due to physical health were significantly lower among participants who responded to placebo, compared with placebo nonresponders. In addition, the overall physical health and 36-item short-form health survey averages were significantly lower. Differences between responders and nonresponders to budesonide did not reach statistical significance. CONCLUSIONS: Lower baseline QOL scores were associated with a clinically significant response to placebo in a trial of treatment for allergic rhinitis. QOL may be a factor in participant response to medication in clinical studies and, hence, a predictor of outcome.

Budesonide↗
PubMed2001

Metformin-associated lactic acidosis in a low risk patient.

Metformin is an oral hypoglycemic agent belonging to the class of biguanides that are commonly used in the treatment of type II diabetes mellitus. Lactic acidosis is a rare but severe adverse reaction that occurs primarily in patients with contraindications such as renal failure. The case of a 71-year-old woman with type II diabetes, in whom severe metformin-associated lactic acidosis was precipitated by acute renal failure in the absence of pre-existing chronic renal failure or other absolute contraindications to biguanide use, is presented. Aggressive correction of the acidosis and prolonged dialysis resulted in a favourable outcome despite severe acidosis. The present case report shows that metformin-associated lactic acidosis can occur in patients without pre-existing renal insufficiency. Metformin should be temporarily stopped when acute renal failure occurs or is anticipated.

Acidosis, Lactic↗
PubMed2000

Coronary angiographic findings and troponin T in patients with unstable angina pectoris.

This study sought to identify differences in coronary anatomic pathology in patients with unstable angina and elevated versus nonelevated serum troponin T values. Previous studies have shown a worse prognosis in unstable angina patients with elevated serum troponin T values. Consecutive patients (n = 117) with Braunwald class IIIB angina were included in the study. Serum samples for troponin T were obtained at admission and every 6 to 8 hours for 18 to 24 hours. Acute myocardial infarction was excluded by routine creatine kinase measurements. All patients underwent coronary angiography before discharge. Cardiac events including cardiac death and myocardial infarction were recorded. Two thirds of the patients with unstable angina had no increase in serum troponin T (<0.1 microg/L) (n = 80). They had a lower incidence of 3-vessel disease (26% vs 46%, p <0.001), left main disease (5% vs 16%, p = 0.04), visible thrombus (4% vs 22%, p = 0.006), and less severe stenosis of the culprit artery (65% vs 84%, p <0.004) than patients with elevated serum troponin T values (> or =0.1 microg/L) (n = 37). The 1-year cardiac event rate was 0% versus 19% in patients with troponin T values <0.1 microg/L compared with patients with serum troponin T values > or =0.1 microg/L (p <0.0001). It was concluded that patients with unstable angina and no release of troponin T have less severe coronary artery disease, and have an excellent prognosis. It is suggested that these patients may be managed more conservatively and without invasive evaluation before discharge.

Adult↗
PubMed2000

Onset of action of intranasal budesonide (Rhinocort aqua) in seasonal allergic rhinitis studied in a controlled exposure model.

BACKGROUND: Intranasal budesonide aqueous nasal spray (BANS) is recognized as an efficacious treatment for seasonal allergic rhinitis (SAR), but the time to onset of action is not known. OBJECTIVE: The primary objective was to evaluate the time at which the onset of action of BANS in the symptomatic relief of seasonal allergic rhinitis becomes evident within 12 hours after a single dose in a controlled ragweed pollen exposure setting. METHODS: The study was of a double-blind, randomized, parallel-group design, testing BANS (64 microgram and 256 microgram) and placebo on ragweed-sensitive subjects with symptoms for at least 1 year by using a controlled pollen challenge system (Environmental Exposure Unit). The efficacy variables were the combined nasal score (the sum of blocked nose, runny nose, and sneezing-itchy nose), individual nasal symptoms, overall evaluation of treatment efficacy reported by participants on diaries, and peak nasal inspiratory flow (PNIF). RESULTS: A total of 217 participants were treated with BANS or placebo. At 7 to 12 hours, BANS was better than placebo in reducing combined nasal and blocked nose symptoms. For PNIF, the time to onset of action was shortest for 256 microgram of BANS relative to placebo (3 hours, P =.003). BANS 64 microgram was better than placebo in reducing the individual scores of blocked nose, runny nose, and sneezing-itchy nose from 3 to 5 hours after administration. Treatment efficacy was higher for those receiving BANS compared with placebo starting at 5 hours. All treatments were well tolerated, and no specific adverse events occurred. CONCLUSIONS: The onset of action of intranasal BANS was 7 hours according to combined nasal and blocked nose symptom scores. Evidence of earlier response was observed at 3 hours for runny nose and PNIF.

Administration, Intranasal↗
PubMed1999

Impact on quality of life during an allergen challenge research trial.

BACKGROUND: Quality of life (QOL) issues resulting from participation in an allergy research trial, or indeed any clinical trial, is not documented in the medical literature. OBJECTIVE: To determine whether participating in a trial where allergic symptoms are induced has a significant impact on subjects' QOL, and to quantify extent and duration. METHODS: Subjects were recruited from a trial utilizing a controlled allergen environment to assess anti-allergic medications. A QOL survey (consisting of the Rhinoconjunctivitis Quality of Life Questionnaire [RQLQ] & the SF-36) was completed at screening, on study day, and approximately 2 weeks post-study. Follow-up was sought from subjects' whose QOL was significantly worse than baseline. RESULTS: Of 219 trial participants, 206 completed both screening and study surveys; 141 returned at least one follow-up survey; and 136 constructed the final dataset. Mean overall scores at follow-up via RQLQ were significantly better than screening (P < .001). Significant decreases in QOL from baseline on study day occurred in social function on the SF-36 (P = .026) and in domains of sleep (P = .019), non-nasal symptoms (P = .05), ocular symptoms (P < .001), and nasal symptoms (P < .001) on the RQLQ. Average post-study follow-up was 17.1 days (range = 5 to 55 days). CONCLUSION: Subjects participating in a trial involving allergic symptom induction experienced a decrease of QOL in parameters specific to rhinoconjunctivitis and social function. Subjects' QOL returned to or improved over baseline within 2 1/2 weeks. Positive QOL findings are important to studies where symptoms are induced and also have relevance to standard Phase 3 drug trials.

Allergens↗
PubMed1997

Onset of action, efficacy, and safety of a single dose of fexofenadine hydrochloride for ragweed allergy using an environmental exposure unit.

BACKGROUND: Fexofenadine hydrochloride is the active acid metabolite of terfenadine. Fexofenadine's anti-allergic properties require confirmation in a clinical setting. OBJECTIVE: The purpose of this study was to characterize the time to onset of clinically important relief of symptoms of allergic rhinitis in subjects taking single doses of either 60 mg or 120 mg fexofenadine HCl, or placebo, after exposure to ragweed pollen in a controlled environment. Other objectives were to assess the efficacy and safety of single doses of fexofenadine HCl. METHODS: One hundred forty-six ragweed-sensitive subjects were primed in the off-season with ragweed pollen in the environmental exposure unit. One hundred thirty-six subjects who adequately responded to priming entered a single-dose placebo phase. Placebo-responders were disqualified from the study, leaving 99 subjects with adequate symptoms to be randomized and given a single dose of either fexofenadine HCl 120 mg (33), 60 mg (33) or placebo (33), after 60 minutes of allergen exposure. Exposure continued over five hours and subjects recorded symptoms every 20 minutes. This study was of a randomized, placebo-controlled, double-blind, parallel design. RESULTS: Median time to onset for relaxed criteria clinically important relief was 60 minutes for both fexofenadine treatment groups, and 100 minutes for placebo (P = .018). The proportion with relief was 82% at 60 mg, 85% at 120 mg, and 64% for placebo. Treated groups had reductions in symptom scores double that of placebo. CONCLUSIONS: Fexofenadine is safe and efficacious at single doses of 60 mg and 120 mg. Average time to onset was 60 minutes using controlled pollen exposure in an environmental exposure unit.

Adolescent↗
PubMed1997

Onset of action and efficacy of terfenadine, astemizole, cetirizine, and loratadine for the relief of symptoms of allergic rhinitis.

BACKGROUND: Terfenadine, astemizole, cetirizine, and loratadine are compared in their abilities to produce relief of symptoms of allergic rhinitis. OBJECTIVE: The aim of this study was to compare the onset of action and efficacy of the study medications. METHODS: 111 ragweed-sensitive subjects were primed with pollen in the Environmental Exposure Unit. Study entry required adequate symptoms over a 3 hour exposure to 5000 +/- 300 grains/m3 of ragweed pollen. On the test day, subjects were given a single dose of either terfenadine 60 mg (22), astemizole 10 mg (22), cetirizine 10 mg (23), loratadine 10 mg (22), or placebo (22) when sufficiently symptomatic after a 60-minute exposure. Allergen levels were maintained and symptoms recorded every 30 minutes. RESULTS: Proportions of subjects with clinically important relief were cetirizine, 69.6%; terfenadine, 54.5%; loratadine, 50.0%; astemizole, 40.9%; and placebo, 31.8% but differences weren't significant between treatment groups (P = .119). Survival curves for times to onset of clinically important relief for the four treatment groups were not different (P = .119). Subjects realizing definitive relief were cetirizine, 65.2%; terfenadine, 45.5%; loratadine, 31.8%; placebo, 27.3%; and astemizole, 22.7% (P = .023). Survival analysis of onset time for definitive relief found significant differences (P = .010). The ranking was cetirizine --> terfenadine --> loratadine --> astemizole (quickest to slowest). Global evaluation based on subject willingness to take the medication again yielded percentages: cetirizine, 82.6%; terfenadine, 66.7%; astemizole, 63.6%; loratadine, 40.9%; and placebo, 36.4% (P = .036). CONCLUSION: Cetirizine and terfenadine continuously ranked higher in terms of onset of action and efficacy, while loratadine and astemizole ranked lower. Significance was detected in definitive relief and relative efficacy.

Adolescent↗
PubMed1995

Cardiac and skeletal muscle myoglobin release after reperfusion of injured myocardium in dogs with systemic hypotension.

BACKGROUND: Myoglobin (Mb) is an intramyocardial protein that is released into the systemic circulation and rapidly cleared via the kidneys after myocardial injury. Arterial Mb concentration-time curves have been studied in humans and dogs in the setting of acute coronary artery occlusion, and the rate of rise of Mb is both sensitive and specific as an indicator of successful coronary artery reperfusion. Systemic hypotension may alter Mb kinetics and impact on the utility of this method by causing Mb release from ischemic skeletal muscle and by decreasing renal Mb clearance. This study was undertaken to determine whether analysis of Mb kinetics remains accurate in identifying coronary reperfusion in the setting of systemic hypotension. METHODS AND RESULTS: Eighteen chronically instrumented dogs were made hypotensive by being bled via a large-bore femoral artery catheter into a reservoir adjusted to maintain a constant mean arterial pressure of 50 mm Hg for 8 hours. After the first hour of hypotension, each dog was studied under one of the following three protocols: group 1, 2 hours of mid-left anterior descending artery (LAD) occlusion followed by 5 hours of unlimited reperfusion; group 2, 7 hours of mid-LAD occlusion without reperfusion; or group 3, 7 additional hours of hypotension alone. Systemic lactate extractions demonstrated a shift to anaerobic metabolism in skeletal muscle and confirmed that shock was established in all animals. Regional arteriovenous Mb differences in group 1 animals demonstrated release of large amounts of Mb from reperfused myocardium; in contrast, smaller amounts of Mb were released both from skeletal muscle rendered ischemic by hypotension and from myocardium rendered ischemic by coronary occlusion without reperfusion. In group 1 dogs, arterial Mb rose rapidly immediately after reperfusion, with peak Mb occurring 108 +/- 24 minutes (mean +/- SEM) after vessel reopening. In group 2 and group 3 dogs, arterial Mb rose more slowly, such that peak Mb was not reached within 8 hours in 11 of 12 animals. The linear rate of rise of arterial Mb over the first hour of reperfusion in group 1 dogs was 51 +/- 16 ng.mL-1.min-1. This slope was significantly greater than slopes determined over the same time period in dogs occluded and not reperfused (group 2, 1.2 +/- 0.6 ng.mL-1.min-1) and in those hypotensive alone (group 3, 0.8 +/- 0.5 ng.mL-1.min-1). All the slopes of group 2 and group 3 dogs fell below the range of slopes of group 1 dogs. In contrast to slopes of the Mb concentration-time curves, linear creatine kinase slopes were significantly less sensitive in predicting reperfusion. CONCLUSIONS: Analysis of plasma Mb kinetics allows early identification of coronary reperfusion after myocardial injury even in the presence of significant systemic hypotension.

Animals↗
PubMed1990

Histamine mediates myocardial damage by an H1 mechanism independent of coronary blood flow.

Administration of histamine to rabbits may result in myocardial damage similar to that produced by catecholamines and the anthracycline antibiotics. To explore the mechanisms involved in histamine-mediated myocardial damage, conscious New Zealand white rabbits were pretreated with H1 and H2 receptor blocking agents, alone and in combination, and then administered histamine. Coronary artery blood flow was measured with radiolabeled microspheres in rabbits that received histamine alone, and in those that received an H1 blocking agent and histamine. Rabbits that received an H1 blocking agent had a significant reduction in morphological injury which was scored as follows: grade 1, minimal or no injury; grade 2, moderate; and grade 3, severe injury (mean pathology score = 1.1 +/- 0.28 for histamine alone vs. 0.06 +/- 0.06 with H1 receptor blockade, p less than 0.05). Animals pretreated with H2 receptor blockade (mean pathology score = 1.2 +/- 0.49) were not protected against morphological injury. Coronary blood flow decreased in animals that received histamine alone: control = 2.61 +/- 0.38 vs. 1.80 +/- 0.30 ml/min/g (p less than 0.05), and in animals pretreated with H1 blockade; control = 3.29 +/- 0.34 vs. 1.91 +/- 0.28 ml/min/g (p less than 0.01). We conclude that histamine-mediated myocardial damage appears to be mediated by the H1 receptor system and that this appears to be independent of initial changes in global coronary blood flow.

Animals↗
PubMed1989

Kinetics of myoglobin release and prediction of myocardial myoglobin depletion after coronary artery reperfusion.

To better define the usefulness of blood myoglobin measurements in evaluating the effectiveness of attempted thrombolysis, we studied the kinetics of myoglobin entry into and removal from the circulation after coronary artery reperfusion and the relation between directly measured depletion of myocardial myoglobin after coronary occlusion and reperfusion and the amount of depletion predicted from plasma myoglobin concentration-time curves. Initially, canine myoglobin was administered to 11 dogs by both bolus injection and 40-minute infusion, and the subsequent disappearance patterns of myoglobin from plasma monitored by radioimmunoassay. A monoexponential regression line (corresponding to a one-compartment model) and a biexponential regression line (corresponding to a two-compartment model) were determined for each set of washout data, the kinetic parameters were calculated, and the goodness of fit of each model was assessed. Results were similar after both methods of myoglobin administration. In five of 11 animals, the one-compartment model described the myoglobin kinetics better; in the other six animals, the two-compartment model was statistically superior, but values for the volume of distribution and elimination rate constant differed by only 10% from the one-compartment estimates. After bolus administration of myoglobin and with a one-compartment model, the volume of distribution of myoglobin was determined to be 1,601 +/- 77 (SEM) ml, representing 6.8 +/- 0.2% of total body weight; the elimination rate constant averaged 0.132 +/- 0.006/min and corresponded to a mean half-time of disappearance of 5.5 +/- 0.2 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Early noninvasive detection of successful reperfusion in patients with acute myocardial infarction.

Myoglobin (Mb) is a protein that enters rapidly and is rapidly cleared from plasma after coronary reperfusion. We sought to determine the accuracy with which a rapid rise in plasma [Mb] could predict successful coronary artery reopening in patients undergoing coronary arteriography in conjunction with attempted reperfusion in acute myocardial infarction. In 42 patients, plasma Mb levels were measured before and for at least 4 hours after attempted reperfusion. Thirty-five patients were successfully reperfused. In each, the plasma Mb level rose rapidly with peak [Mb] occurring at 111 +/- 8.1 (+/- SEM) minutes after application of therapy. In contrast, Mb levels rose more slowly in the seven patients who were not reperfused, with peak [Mb] occurring 360 +/- 61.4 minutes after attempted reperfusion. T25-100 (the time required for [Mb] to rise from 25% to 100% of peak value) was shorter in patients successfully reperfused (71 +/- 7.9 minutes) and longer (341 +/- 35.3 minutes) in patients in whom therapy was unsuccessful. A rapid rise in [Mb] after successful reperfusion was also evident by a more than 4.6-fold rise in [Mb] over the first 2 hours after reperfusion in all but five patients; in contrast, [Mb] rose by less than 4.6-fold over this same interval in every patient not successfully reperfused (sensitivity, 85%; specificity, 100%; predictive accuracy, 88%). We conclude that a rapid rise in plasma Mb level over the initial 2 hours after attempted reperfusion in acute myocardial infarction provides a useful index of successful reperfusion.

Adult↗
PubMed1987

Interpretation of changes in coronary flow that accompany pharmacologic interventions.

The interpretation of a change in coronary flow that accompanies administration of a calcium-entry blocker or other pharmacologic agent remains complicated by the variety of factors potentially altered by the agent that can themselves affect flow. These factors are reviewed in the context of steady-state coronary pressure-flow relationships, emphasizing the complexities induced by coronary artery disease. Limitations of currently available approaches for the measurement of coronary reserve, examination of flow heterogeneity, and the calculation of coronary vascular resistance are also addressed. Calcium entry-blocking agents have a number of hemodynamic effects that are likely to augment coronary flow favorably. However, parodoxical and potentially deleterious effects on local flow also seem possible in selected situations.

Animals↗
PubMed1985

Patterns of myoglobin release after reperfusion of injured myocardium.

Myoglobin is an intracardiac protein that is released into the blood after myocardial injury and is then cleared rapidly by the kidneys. This study was undertaken to determine whether successful reperfusion of damaged myocardium could be assessed by examination of blood myoglobin concentration-time patterns. After release of a 2 hr occlusion of the mid left anterior descending coronary artery in 11 dogs that had been instrumented over the long term, immunoreactive arterial plasma concentration of myoglobin, [Mb], rose rapidly to a peak within 25 +/- 2(SEM) min (range 20 to 40). Individual peaks were three to 165 times the myoglobin levels immediately before release of the occlusion. Myoglobin was cleared rapidly from plasma, falling to one-half its peak level 38 +/- 3 min after the peak. Similarly well-defined peaks in [Mb] were evident in plasma from the great cardiac vein (GCV), with a mean time to peak of 16 +/- 2 min and a magnitude of two to 177 times prerelease values. In contrast, arterial and GCV creatine kinase activity-time curves showed less defined peaks and they occurred later and with more variability (60 to 330 min after reperfusion). In nine patients with acute infarction, successful coronary artery reopening was also accompanied by a sharp four- to sixteenfold rise in plasma [Mb] within 1 to 2 hr. Elevations in plasma creatine kinase were slower and more prolonged, peaking at 2 to 18 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Coronary pressure-flow relationships. Controversial issues and probable implications.

On the basis of the material discussed, our current assessments of the controversial points mentioned at the beginning of this article may be summarized as follows: Pf = 0, the minimum back pressure to coronary flow associated with a measurable conductance, is indeed greater than coronary outflow pressure (and usually left ventricular diastolic pressure, as well). Pf = 0 needs to be taken into account in attempts to determine coronary driving pressure. In maximally vasodilated beds, Pf = 0 derived from diastolic pressure-flow relationships exceeds coronary outflow pressure by at least a few mm Hg. Pf = 0 varies with coronary outflow and/or diastolic ventricular cavity pressure. When left ventricular preload is elevated, Pf = 0 exceeds outflow pressure by increasing amounts. Pf = 0 appears to be systematically higher and pressure-dependent in beds in which vasomotor tone is operative. An improved understanding of the nature of, and basis for, time-dependent changes in resistance and/or Pf = 0 during long diastoles in nonvasodilated beds is needed. The contour of pressure-flow relationships which are free of reactive effects is curvilinear rather than linear. The degree of curvilinearity is substantial and can change with interventions. Curvilinearity is accentuated at lower pressures and may reflect changes in the number of perfused vascular channels as well as the caliber of individual channels. Capacitive effects need to be dealt with quantitatively in studies of pressure-flow relationships. Values of the capacitance which is involved in these effects vary with both pressure and tone. Capacitive flow also depends upon the instantaneous rate of change of pressure, which has not usually been defined in published studies. Although intramyocardial capacitance is large and plays an important role in systolic-diastolic flow interactions, a controlling role in diastolic coronary arterial pressure-flow relationships has not been established experimentally. In vasodilated beds, in-flow remains remarkably constant for several seconds after the brief transient associated with a step-change in the level of constant pressure perfusion during a long diastole. Calculations of coronary vascular resistance (by whatever method) remain of limited value, particularly when changes in response to an intervention are modest. Because of the curvilinear diastolic pressure-flow relationship, resistance is pressure-dependent and, at any given pressure, is probably best defined by establishing the slope of a diastolic pressure-flow curve which is free of reactive effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Reduction of ischemic depolarization by the calcium channel blocker diltiazem. Correlation with improvement of ventricular conduction and early arrhythmias in the dog.

Calcium channel blockers suppress early ischemic arrhythmias, possibly by diminishing intracellular calcium overload and its effect on the ventricular action potential. To explore this, we compared the effects of diltiazem on ischemic "injury" potentials and ventricular fibrillation during serial coronary artery occlusions in dogs. Injury potentials and ventricular fibrillation were elicited every 15-25 minutes by simultaneous occlusion of the left anterior descending and circumflex arteries during rapid atrial pacing. DC epicardial electrograms were recorded differentially between the ischemic region and a small nonischemic region supplied by a proximal branch of the left anterior descending artery. Injury potentials developed with a uniform time course during five control occlusions, but were reduced by diltiazem infusion (0.5 mg/kg over 25 minutes) in each of eight dogs. The mean diastolic injury potential (T-Q depression) at 150 seconds of ischemia was 9.1 +/- 2.7 mV before diltiazem and 6.1 +/- 1.6 mV afterward (P less than 0.001). Diltiazem increased the mean time between coronary occlusion and ventricular fibrillation from 186 to 366 seconds (P less than 10(-5), but did not change the magnitude of the diastolic injury potential at onset of ventricular fibrillation. Diltiazem also delayed ischemia-induced conduction impairment to the same extent that it delayed injury potential development. In five dogs, the effect of diltiazem on regional blood flow near the epicardial electrodes was measured by infusion of radionuclide-labeled microspheres. Coronary occlusion reduced flow to the ischemic zone from 0.86 to 0.05 ml/min per g (P = 0.001). Diltiazem increased preocclusion flow by 11% (P = 0.03), but did not significantly alter flow during occlusion. Hemodynamic measurements show that diltiazem did not diminish cardiac work. Diltiazem therefore produced a flow-independent reduction of cellular depolarization during ischemia, which may be due to relief of calcium overload, and which may explain the antifibrillatory effect.

Action Potentials↗
PubMed1981

Zero-flow pressures and pressure-flow relationships during single long diastoles in the canine coronary bed before and during maximum vasodilation. Limited influence of capacitive effects.

The proposal that diastolic coronary flow is regulated by an intramyocardial "back-pressure" that substantially exceeds coronary venous and ventricular diastolic pressures has been examined in an open-chest canine preparation in which instantaneous left circumflex pressure and flow could be followed to cessation of inflow during prolonged diastoles. Despite correlation coefficients consistently >0.90, pressure-flow data during individual diastoles were concave to the flow axis before and during pharmacologically induced maximum coronary vasodilation. Data were better fitted (P < 0.01) by second-order equations than by linear equations in >90% of cases. Second-order pressure-axis intercepts (P(f=0))(1) averaged 29+/-7 (SD) mm Hg before vasodilation and 15+/-2 mm Hg during vasodilation; left and right atrial pressures were always substantially lower (8+/-3 and 5+/-2 mm Hg before vasodilation and 8+/-2 and 4+/-1 mm Hg during dilation). Values of P(f=0) before vasodilation varied directly with levels of coronary inflow pressure. A modification of the experimental preparation in which diastolic circumflex pressure could be kept constant was used to evaluate the suggestion that P(f=0) measured during long diastoles are misleadingly high because of capacitive effects within the coronary circulation as inflow pressure decreases. Decreases in P(f=0) attributable to capacitive effects averaged only 5.9+/-3.0 mm Hg before vasodilation and were smaller during dilation. We conclude that P(f=0) is a quantitatively important determinant of coronary driving pressure and flow, resulting from both factors related to, and independent of, vasomotor tone. Adjustments of flow during changing physiological situations may involve significant changes in P(f=0) as well as in coronary resistance.

Animals↗