Coronary stenting without predilatation (SWOP): applicable technique in everyday practice.

To evaluate the feasibility of stenting without predilatation, we registered all interventional procedures over a 6-month period. Six hundred patients were registered, and 684 lesions were treated. Interventions were divided into four groups: stenting without predilatation (SWOP), 221 lesions (32.4%); primary stenting with predilatation (PDS), 161 lesions (23.5%); provisional stenting (PRS), 131 lesions (19.2%); and plain-old balloon angioplasty (POBA), 171 lesions (25%). Interventional strategy was at the discretion of the operator based on few simple angiographic criteria and his clinical judgment. Procedural success was similar in all stent groups. We conclude that when primary stenting is planned, about 60% of lesions can be treated by SWOP effectively with excellent procedural results and considerable cost saving.

Surgical removal of stent entrapped in proximal left coronary artery system.

Coronary artery stents were developed to prevent acute coronary closure and reduce restenosis after coronary angioplasty. A well-recognized, although uncommon, complication of stent deployment is loss of control, resulting in the stent being inadvertently deployed in an undesirable location. This case study describes a patient who underwent stent insertion to the left anterior descending artery and had stent entrapment in the left anterior descending/left main coronary artery. The stent was surgically removed, preventing unnecessary bypass grafting to a normal circumflex artery.

An unusual cause of recurrent angina two years after coronary artery bypass grafting: fistula between internal mammary artery graft to pulmonary vasculature.

A 55-year-old man developed recurrent angina pectoris 2 years after coronary artery bypass grafting. Cardiac catheterization demonstrated that the venous grafts were patent, but selective left internal mammary angiogram showed multiple fistulous connections between the internal mammary artery and the pulmonary vasculature of the left upper lobe. After surgical correction of the fistula, the angina resolved. Only three previous cases of acquired internal mammary artery graft fistulas draining to the pulmonary vasculature have been described. The etiology, clinical presentation, and management of an internal mammary artery fistula to the pulmonary vasculature are discussed.

Ischemia and reperfusion during intermittent coronary occlusion in man. Studies of electrocardiographic changes and CPK release.

The course of 357 balloon inflations performed during 38 angioplasties for single-vessel coronary artery disease was prospectively studied using continuous ECG recording. Ischemic ECG changes appeared during 91 percent of the inflations at a mean of 20 +/- 8 seconds after inflation and resolved in 97 percent of those at a mean of 11 +/- 5 seconds after deflation. Elevation of the plasma CPK level was found in six patients who had ischemic ECG changes for at least 7.8 minutes. The duration of ischemia did not exceed 5.4 minutes in any of the patients without CPK elevation. Resolution of the ischemic changes was delayed in patients with CPK elevation and in last vs initial inflations. We conclude that in patients with noninfarcted myocardium, ECG changes follow coronary occlusion and reflow very rapidly, detecting these coronary events with a high sensitivity. Lack of rapid regression predicts lack of reperfusion, and persistence of ischemia for more than 7.8 minutes is sufficient to cause myocardial necrosis.

Hypocapnia does not alter collateral ventilation in sheep.

Hypocapnic constriction has been proposed as a mechanism by which collateral pathways might rapidly alter ventilation to match perfusion. We studied the changes in response to hypocapnia with age in sheep, a species with collateral resistance (Rcoll) similar to those measured in humans. Measurements of Rcoll were made with either 5 or 10% CO2 and with air (hypocapnia) in 29 anesthetized sheep, ages 6 mo to 10 yr, with the wedged bronchoscope technique. Rcoll was 0.42 +/- 0.12, 0.58 +/- 0.18, 0.32 +/- 0.18, and 0.17 +/- 0.04 (SE) cmH2O.ml-1.min in 6-mo- and 1-, 2-, and 10-yr-old animals, respectively. These values were unchanged with hypocapnia. Despite the lack of a change in Rcoll with hypocapnia, administration of histamine aerosol (8 animals) through the bronchoscope increased Rcoll by 151 +/- 35% (P less than 0.05). These data suggest that although collateral pathways exist in sheep and are capable of constriction, they do not respond to hypocapnia. Furthermore, the response to hypocapnia is not influenced by age.

Protective role of epithelium in the guinea pig airway.

We developed an in vitro system to assess the role of the epithelium in regulating airway tone using the intact guinea pig trachea (J. Appl. Physiol. 64: 466-471, 1988). This method allows us to study the response of the airway when its inner epithelial surface or its outer serosal surface is stimulated independently. Using this system we evaluated how the presence of intact epithelium can affect pharmacological responsiveness. We first examined responses of tracheae with intact epithelium to histamine, acetylcholine, and hypertonic KCl when stimulated from the epithelial or serosal side. We then examined the effect of epithelial denudation on the responses to these agonists. With an intact epithelium, stimulation of the inner epithelial side always caused significantly smaller changes in diameter than stimulation of the outer serosal side. After mechanical denudation of the epithelium, these differences were almost completely abolished. In the absence of intact epithelium, the trachea was 35-fold more sensitive to histamine and 115-fold more sensitive to acetylcholine when these agents were applied to the inner epithelial side. In addition, the presence of an intact epithelium almost completely inhibited any response to epithelial side challenge with hypertonic KCl. These results indicate that the airway epithelial layer has a potent protective role in airway responses to luminal side stimuli, leading us to speculate that changes in airway reactivity measured in various conditions including asthma may result in part from changes in epithelial function.

In vivo exposure to ozone causes increased in vitro responses of small airways.

We examined the effects of in vivo exposure to 3 ppm ozone on in vitro reactivity of large and small airways from dogs. No effects in large airways were detected. However, small airways exposed to O3 had larger responses to receptor-mediated stimuli and similar responses to KCl plus phorbol ester. These results suggest that small airways are more vulnerable to O3 inhalation than are large airways and that receptor-mediated pathways reflect that sensitivity. Another possible explanation is that O3 exposure prevents the epithelium from playing its normal dampening role in responses to contractile agonists.

Prolonged increased responsiveness of canine peripheral airways after exposure to O3.

Because it is relatively insoluble, the oxidant gas O3 may penetrate to small peripheral airways when it is inhaled. Increased responsiveness in large airways after O3 breathing has been associated with the presence of inflammatory cells. To determine whether O3 produces prolonged hyperresponsiveness of small airways associated with the presence of inflammatory cells, we exposed the peripheral lungs of anesthetized dogs to 1.0 ppm O3 for 2 h using a wedged bronchoscope technique. A contralateral sublobar segment was simultaneously exposed to air as a control. In the O3-exposed segments, collateral resistance (Rcs) was increased within 15 min and remained elevated approximately 150% throughout the 2-h exposure period. Fifteen hours later, the base-line Rcs of the O3-exposed sublobar segments was significantly elevated, and these segments demonstrated increased responsiveness to aerosolized acetylcholine (100 and 500 micrograms/ml). There were no differences in neutrophils, mononuclear cells, or mast cells (numbers or degree of mast cell degranulation) between O3 and air-exposed airways at 15 h. The small airways of the lung periphery thus are capable of remaining hyperresponsive hours after cessation of localized exposure to O3, but this does not appear to be dependent on the presence of inflammatory cells in the small airway wall.

Osmotic stimuli induce epithelial-dependent relaxation in the guinea pig trachea.

Epithelium in airways, like endothelium in blood vessels, may regulate responses of adjacent smooth muscle. To study the intact trachea from guinea pigs we developed an in vitro preparation that permits independent stimulation from either the inner epithelial surface or the outer serosal surface. The whole guinea pig trachea was excised, cannulated, and perfused at a constant flow with Krebs-Henseleit (KH) solution that was in direct contact with the inner epithelial-lined surface. The outer serosal surface of the trachea was immersed in a separate system (bath) containing KH solution. Tracheal responses were assessed by measuring the pressure drop between the tracheal inlet and the outlet under conditions of constant flow. When the trachea was precontracted with carbachol or KCl, hyperosmolar stimuli (KCl, mannitol, urea, or NaCl) produced concentration-dependent relaxation when applied to the inner epithelial surface. Relaxation was not produced when the hyperosmolar stimulus was applied to the serosal surface and was markedly reduced or abolished when the epithelial surface had been physically damaged or removed. These results indicate that hyperosmotic stimuli induce epithelial-dependent relaxation of trachea. A defect in this mechanism may be partially responsible for the bronchoconstriction seen in asthmatic subjects after exercise.

Aminophylline reduces air-flow-induced constriction in the canine lung periphery.

We examined the effect of aminophylline on air-flow-induced constriction in the canine lung periphery. A wedged bronchoscope technique was used to measure airway wall temperature (Taw) and collateral resistance (Rcs) before and after air flow was increased from a baseline flow of 200 to 500, 1,000, 1,500, or 2,000 ml/min for 2-min periods. When a sublobar segment was challenged with dry air, Taw fell during the challenge (p less than 0.05) and Rcs increased 5 min postchallenge (p less than 0.01). Pretreatment with aminophylline (20 mg/kg) reduced the fall in Taw by 31% and reduced the increase in Rcs by 53%. Aminophylline did not significantly affect either the concentrations of PGD2, TxB2, and histamine or the cell numbers and profiles obtained by bronchoalveolar lavage performed 5 min postchallenge. However, trends were consistent with the decreased physiologic responses observed. Finally, aminophylline proved ineffective in reducing the constrictor response of peripheral lung challenged directly with aerosolized histamine or PGD2. Because preaminophylline and postaminophylline peripheral lung sensitivity (as assessed by the ratio delta Rcs/delta Taw) were not significantly different, we conclude that aminophylline attenuates physiologic responses by reducing the strength of the stimulus. Aminophylline could do this by facilitating the replacement of heat and water removed during dry air challenge by increasing bronchial or pulmonary blood flow, or by reducing heat and water loss via changes in mucosal permeability.

Protein kinase C and tracheal contraction at low temperature.

During exercise or dry air-induced asthma, airway walls cool. However, the role of temperature in the regulation of airway tone is not clear. Protein kinase C (PKC) is an important second messenger in the mediation of cell responses. To explore whether changes in temperature affect pathways involving PKC in airways, we examined the effects of phorbol esters, potent activators of PKC, in guinea pig tracheal rings at various temperatures. Phorbol-12,13-diacetate (PDA) caused a reduction in tracheal tone at 37 degrees C and an increase in tone when temperature was reduced to 22 degrees C. Increases in tone were also produced by PDA when cell membranes were depolarized by ouabain (10 microM) or KCl (30 mM) at 37 degrees C. Contractions produced by PDA at 22 degrees C were inhibited by lipoxygenase inhibitors [ETYA (5,8,11,14-eicosatetraynoic acid), NDGA (nordihydroguaiaretic acid) and phenidone] and a leukotriene receptor antagonist [FPL 55712 (sodium 7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)-2-hydroxypropoxyl] -4-oxo-8-propyl-4H-1-benzopyran-2-carboxylate)]. Contractions produced by PDA at 37 degrees C or 22 degrees C in the presence of ouabain (10 mM) or KCl (30 mM) were not affected by these drugs. These results indicate that changes in temperature have profound effects on responses resulting from PKC activation. At low temperature, the lipoxygenase pathway mediates responses. Thus, cooling has the potential to modify a major intracellular pathway regulating physiological responses of the airways.

Airflow-induced bronchospasm. Imbalance between airway cooling and airway drying?

We used an animal model of airflow-induced bronchospasm (AIB) to examine the role of airway cooling in responses to dry air challenge. A bronchoscope was wedged in situ into perfused lower lobes of anesthetized dogs. Through the bronchoscope, dry air was delivered, resistance to collateral flow (Rcs) was measured, and airway wall temperature (Taw) was monitored. A dry-air challenge through the bronchoscope produced a fall in Taw and a rise in Rcs, presumably related to evaporative heat loss (EHL) and/or an increase in osmolarity. By changing the temperature of blood perfusing the lobe it was possible to lower Taw without affecting either EHL or osmolarity. Four series of experiments were performed. In the first series, Taw was lowered in 2 ways: by increasing dry air flow and by cooling the pulmonary perfusate. After a 2-min challenge with dry air, Rcs rose. After lowering Taw with cooled blood for 2 min, Rcs did not rise. In the second series of studies, Taw was lowered for 15-min periods by reducing the temperature of blood. Neither cooling per se nor rewarming after the 15 min of cooling initiated increases in lung tone. In the third series of experiments, a 2-min dry air challenge was performed while the lobe was perfused with cool blood. Despite greater reductions in Taw during the dry-air challenge, responses after the challenge were virtually abolished. In a final series of experiments in which pulmonary perfusion was stopped during challenge, airway cooling was enhanced, and responses were again significantly attenuated. Thus, cooling actually depressed increases in Rcs produced by dry-air challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypocapnia-induced constriction of the canine peripheral airways exhibits tachyphylaxis.

Hypocapnia-induced constriction of peripheral airways may be important in regulating the distribution of ventilation in pathological conditions. We studied the response of the peripheral lung to hypocapnia in anesthetized, paralyzed, mechanically ventilated dogs using the wedged bronchoscope technique to measure resistance of the collateral system (Rcs). A 5-min hypocapnic challenge produced a 161 +/- 19% (mean +/- SE) increase in Rcs. The magnitude of this response was not diminished with repeated challenge or by atropine sulfate (1 mg base/kg iv), chlorpheniramine maleate (5 mg base/kg iv), or indomethacin (5 mg/kg iv). The response was reduced by 75% by isoproterenol (5 micrograms/kg iv) (P less than 0.01) and reduced by 80% by nifedipine (20 micrograms/kg iv) (P less than 0.05). During 30-min exposure to hypocapnia the maximum constrictor response occurred at 4-5 min, after which the response attenuated to approximately 50% of the maximum response (mean = 53%, range 34-69%). Further 30-min challenges with hypocapnia resulted in significantly decreased peak responses, the third response being 50% of the first (P less than 0.001). The inability of indomethacin or propranolol to affect the tachyphylaxis or attenuation of the response suggests that neither cyclooxygenase products nor beta-adrenergic activity was involved. Hence, hypocapnia caused a prompt and marked constrictor response in the peripheral lung not associated with cholinergic mechanisms or those involving histamine H1-receptors or prostaglandins. With prolonged exposure to hypocapnia there was gradual attentuation of the constrictor response with continued exposure and tachyphylaxis to repeated exposure both of which would tend to diminish any compensatory effect of hypocapnic airway constriction on the distribution of ventilation.

Dry air-induced constriction: effects of pharmacological intervention and temperature.

We studied airway wall temperature (Taw) during dry air challenge of the canine lung periphery. We measured collateral resistance (Rcs) before and after periods of elevated airflow using a wedged bronchoscope technique. As flow rate increased, Taw dropped and postchallenge Rcs rose. A significant negative correlation was found between Taw recorded during challenge and Rcs observed 5 min after challenge. Repetitive dry air challenge produced similar changes in Rcs and Taw. However, responses to warm moist air were significantly lower than consecutive responses to dry air. Taw was significantly lower during dry air challenge than during moist air challenge. Indomethacin (5 mg/kg) and atropine (1 mg/kg) reduced responses to dry airflow challenge. Indomethacin did not affect Taw during the challenge, whereas atropine reduced the fall in Taw. We conclude that temperature correlates negatively with peripheral lung tone 5 min after dry air challenge. This correlation holds under conditions where airflow is increased, air is humidified, or atropine is administered. The dissociation between Taw and physiological response after indomethacin likely reflects a decrease in mediators released during challenge.

Effects of maturation and aging on collateral ventilation in sheep.

We studied collateral ventilation as a function of age by measuring the resistance (Rcoll) and time constant (Tcoll) of collateral airflow in young (2-10 mo), mature (16-24 mo), and old sheep (6-13 yr). Rcoll was 0.50 +/- 0.11 cmH2O X ml-1 X min (SE) in young sheep and decreased significantly to 0.05 +/- 0.02 and 0.02 +/- 0.01 cmH2O X ml-1 X min in mature and old sheep, respectively. Tcoll was 34.4 +/- 7.9 (SE) s in young sheep and decreased to 5.7 +/- 0.9 and 10.2 +/- 3.1 s in mature and old sheep, respectively. We conclude that a marked decrease in Rcoll and Tcoll occurs between birth and maturity but changes little with further aging. In the young an increased resistance and time constant of collateral airflow may accentuate ventilation perfusion imbalance and impair the removal of secretions in disease states.

Airflow-induced bronchoconstriction: role of epithelium and eicosanoid mediators.

We examined the role of cyclooxygenase-derived metabolites and epithelial cells in airflow-induced bronchospasm. Male dogs were anesthetized and collateral system resistance (Rcs) was measured with the wedged-bronchoscope technique. A 2-min high flow challenge with dry air in nine animals produced a mean increase in Rcs of 69 +/- 13% (SE). After treatment with indomethacin (5 mg/kg), the response was significantly attenuated; Rcs increased only 40 +/- 8%. Bronchoalveolar lavage performed 5 min after a dry air challenge yielded fluid with greater concentrations of prostaglandin D2 (PGD2) and thromboxane B2 than samples from unchallenged segments. Challenge with humidified air produced a smaller physiological response than did challenge with dry air. Lavage samples obtained after dry challenge had greater concentrations of PGD2 than samples taken after challenge with humidified air. After dry air challenge, epithelial cells in lavage fluid were increased by 454 and 515% when compared with control and humidified air challenge, respectively. Significant correlations were found between epithelial cell number and PGD2 recovered in lavage fluid after dry air challenges. We conclude that both epithelial cells and prostaglandins play an important role in peripheral lung responses to dry air.

Lithium dampens neurotransmitter response in smooth muscle: relevance to action in affective illness.

Lithium, by inhibiting inositol phosphate metabolism, interferes with the phosphatidylinositol ("phosphoinositide") cycle, which is stimulated by numerous hormones and neurotransmitters. To examine the relevance of this action to neurotransmission, we evaluated effects of lithium treatment on smooth muscle responses to transmitters. In lithium-pretreated tracheal muscle, the relaxation following carbachol or histamine contractions is retarded. Lithium does not affect relaxation following contractions elicited by treatment with KCl and phorbol 12,13-diacetate in combination, which bypasses receptor stimulation of the phosphatidylinositol cycle. Half-maximal effects of lithium occur at 1 mM, corresponding to therapeutic concentrations. Dampening of neurotransmitter responses by lithium treatment may explain the unique ability of lithium to relieve and prevent both mania and depression.

Perfusion of lung periphery: effects of local exposures to ozone and pressure.

Following ozone (O3) exposure, airways reactivity increases. We investigated the possibility that exposure to O3 causes a decrease in pulmonary perfusion, and that this decrease is associated with the increase in reactivity. Perfusion was measured with radiolabeled microspheres. A wedged bronchoscope was used to isolate sublobar segments in the middle and lower lobes of anesthetized dogs. Isolated segments were exposed to either O3 or an elevated alveolar pressure. Although increased alveolar pressure decreased microsphere density, exposure to 1 ppm O3 did not. Collateral system resistance rose significantly following exposure to O3 and to high pressure. These studies do not support the hypothesis that pulmonary perfusion is decreased following O3 exposure and is associated with subsequent increases in reactivity.

Interstitial fibrosis and collateral ventilation.

Interstitial fibrosis may increase resistance to collateral flow (Rcoll) because of decreased lung volume and destruction of collateral channels or it may decrease Rcoll because of emphysematous changes around fibrotic regions. In addition, if interstitial fibrosis involves a small region of lung periphery, interdependence from surrounding unaffected lung should produce relatively large changes in volume of the fibrotic region during lung inflation. We studied the effects of interstitial fibrosis on collateral airflow by measuring Rcoll at functional residual capacity (FRC) in nine mongrel dogs before and 28 days after the local instillation of bleomycin into selected lung segments. In six of these dogs Rcoll was also measured at a higher lung volume (transpulmonary pressure = 12 cmH2O above FRC pressure). Rcoll increased in fibrotic lung segments following local treatment with bleomycin. With lung inflation (high transpulmonary pressure) Rcoll fell a similar proportion in fibrotic and nonfibrotic lung regions. These observations suggest that collateral resistance increases in fibrotic segments because lung volume decreases or because collateral pathways are involved directly in the fibrotic process. Compensatory increases in collateral communications do not occur. In addition, pulmonary interdependence does not cause disproportionate increases in volume and decreases in Rcoll of the fibrotic region during lung inflation.