Daniel L. Levin

Morphologic analysis of the pulmonary vascular bed in congenital left-sided diaphragmatic hernia*

The contribution of an abnormal pulmonary vascular bed to right-to-left shunting in patients with congenital left-sided diaphragmatic hernia and alveolar hypoplasia has not been defined. In three infants we analyzed lungs fixed by perfusion. Left lung volumes (ml/kg birth weight) were 1.7, 6.5 and 4.0 respectively (control = 11.7) and right lung volumes 5.7, 11.7 and 9.8 respectively (control = 14.3). Serial sections were prepared and fifth generation (resistance) vessels identified. Compared to control the medial widths were increased in all lungs and the medial width/external diameter ratios were increased in the left lungs of two patients and the right lung of one. The m/d ratio in the left lung was greater than that in the right lung in two of the three patients. There were fewer pulmonary vessels/cm2 lung tissue in the study lungs than in the control lung, and there were significantly fewer pulmonary vessels/cm2 lung tissue in the left than in the right lung in two of the three patients. Although there was increased smooth muscle in resistance vessels, intravenous therapy with tolazoline HCl did not improve systemic oxygenation. We conclude that this was probably due to the decreased total size of the pulmonary vascular bed and the decreased number of pulmonary vessels per unit lung tissue, causing a fixed high pulmonary vascular resistance.

Morphologic analysis of the pulmonary vascular bed in infants exposed in utero to prostaglandin synthetase inhibitors

Since the effects of prostaglandin synthetase inhibitors on the developing human fetal pulmonary vasculature are unknown, we studied the lungs of two infants, one whose mother took salicylates and the other whose mother took indomethacin during pregnancy. Lungs were fixed by perfusion and fifth generation (resistance) vessels identified. The infant with chronic exposure to aspirin had premature constriction of the ductus arteriosus, tricuspid insufficiency, increased pulmonary arterial medial width/external diameter ratio due to increased smooth muscle, and a decreased number of pulmonary vessels/cm2 lung tissue. The infant with short-term exposure to indomethacin had hypoxemia, increased pulmonary arterial m/d ratio due to increased smooth muscle, and a normal number of pulmonary vessels/cm2 lung tissue. These abnormalities may be due to the effects of prostaglandin synthetase inhibitor drugs on the ductus arteriosus and/or the pulmonary vessels of the human fetus.

Matrix Metalloproteinase-28 Deletion Exacerbates Cardiac Dysfunction and Rupture After Myocardial Infarction in Mice by Inhibiting M2 Macrophage Activation

Rationale: Matrix metalloproteinase (MMP)-28 regulates the inflammatory and extracellular matrix responses in cardiac aging, but the roles of MMP-28 after myocardial infarction (MI) have not been explored. Objective: To determine the impact of MMP-28 deletion on post-MI remodeling of the left ventricle (LV). Methods and Results: Adult C57BL/6J wild-type (n=76) and MMP null (MMP-28−/−, n=86) mice of both sexes were subjected to permanent coronary artery ligation to create MI. MMP-28 expression decreased post-MI, and its cell source shifted from myocytes to macrophages. MMP-28 deletion increased day 7 mortality because of increased cardiac rupture post-MI. MMP-28−/− mice exhibited larger LV volumes, worse LV dysfunction, a worse LV remodeling index, and increased lung edema. Plasma MMP-9 levels were unchanged in the MMP-28−/− mice but increased in wild-type mice at day 7 post-MI. The mRNA levels of inflammatory and extracellular matrix proteins were attenuated in the infarct regions of MMP-28−/− mice, indicating reduced inflammatory and extracellular matrix responses. M2 macrophage activation was impaired when MMP-28 was absent. MMP-28 deletion also led to decreased collagen deposition and fewer myofibroblasts. Collagen cross-linking was impaired as a result of decreased expression and activation of lysyl oxidase in the infarcts of MMP-28−/− mice. The LV tensile strength at day 3 post-MI, however, was similar between the 2 genotypes. Conclusions: MMP-28 deletion aggravated MI-induced LV dysfunction and rupture as a result of defective inflammatory response and scar formation by suppressing M2 macrophage activation.

Dobutamine: A hemodynamic evaluation in children with shock*

The hemodynamic effects of dobutamine were studied in 33 infants and children with cardiogenic or septic shock. Dobutamine was administered at doses of 2.5, 5.0, 7.5, and 10.0 micrograms/kg/minute. Significant increases above preinfusion values were observed in cardiac index, left ventricular stroke work index, and pulmonary wedge pressure. Significant decreases from preinfusion values were observed in systemic arteriolar resistance index. No significant differences occurred in heart rate, mean systemic arterial pressure, mean pulmonary arterial pressure, right atrial pressure, or pulmonary arteriolar resistance index. Analysis of the data also revealed significant effects of age and diagnosis on the hemodynamic responses. These data suggest that dobutamine is a useful drug in the pharmacologic management of children in shock, especially in children older than 12 months with cardiogenic shock not complicated by severe hypotension.

Constriction of the fetal ductus arteriosus after administration of indomethacin to the pregnant ewe

The prostaglandin synthetase inhibitor indomethacin was given orally or intravenously to pregnant ewes. This resulted in the fetal pulmonary to systemic arterial mean blood pressure difference across the ductus arteriosus rising significantly, presumably secondary to constriction of the ductus arteriosus. The pressure difference was due to pulmonary arterial hypertension, and not due to a fall in systemic arterial mean blood pressure. Fetal arterial blood gas tensions and pH values were normal throughout. In five experiments the pressure difference could be promptly but temporarily reversed by the administration of PGE1 into the fetal inferior vena cava. Indomethacin was present in fetal blood, and maternal plasma prostaglandin levels were suppressed. Indomethacin administration during pregnancy causes constriction of the fetal ductus arteriosus and fetal pulmonary arterial hypertension which, if severe, may cause rapid fetal death. It is possible that this mechanism may be one cause of persistent pulmonary hypertension or tricuspid insufficiency or both in the newborn infant.

Pulmonary microthrombi syndrome in newborn infants with unresponsive persistent pulmonary hypertension

Some newborn infants with either primary or secondary persistent pulmonary hypertension (PPHN) remain hypoxemic, hypercarbic, and acidotic despite therapeutic efforts. In autopsies of 23 infants who had PPHN, diffuse platelet-fibrin thrombi were present in the pulmonary microcirculation of eight (15.2 +/- 18.1 thrombi/cm2 lung tissue) and absent in 15 (0.2 +/- 0.3 thrombi/cm2 lung tissue), (P less than 0.004). Diagnoses in group A (thrombi) were pneumonia and sepsis (four patients), meconium inhalation (3), and primary PPHN (1); and in group B (no thrombi) pneumonia and sepsis (4), meconium inhalation (4), primary PPHN (4), hyaline membrane disease (2), and diaphragmatic hernia (1). The only significant differences between the two groups were the response to tolazoline infusion as assessed by changes in partial pressure of arterial oxygen (PaO2) and the platelet counts. Group A responded less favorably to tolazoline (14.8 mm Hg vs 83.6 mm Hg; P less than 0.05) and had lower platelet counts (51,000/microliter vs 128,000/microliter) (P less than 0.01) than group B. No significant differences could be detected in Apgar scores, duration or mode of mechanical ventilation, oxygen requirements, arterial blood gas tensions or pH, systemic arterial blood pressure, coagulation profile, amount of blood product transfusions, or intravascular catheter use. Pulmonary microthrombi should be added to the list of mechanisms for PPHN and may explain why some infants do not respond well to therapeutic efforts aimed at vasodilation. Thrombocytopenia and failure to respond to pulmonary vasodilators might suggest the diagnosis.

Acute kidney injury following peripheral angiography and endovascular therapy: A systematic review of the literature.

Radiographic contrast administration is a major cause of acute kidney injury (AKI), worldwide. Currently, contrast induced acute kidney injury (CI‐AKI) is the third leading cause of hospital acquired renal failure in the United States. Over 50% of these cases are the result of contrast exposure during cardiac catheterization. The predictive risk factors for and clinical impact of AKI following coronary procedures have been extensively studied and documented in the literature. Similar data, however, are lacking for AKI following angiography or endovascular interventions for lower extremity peripheral artery disease (PAD).

Pseudomonas aeruginosa Corneal Infections in Seriously Ill Children

Bacterial corneal ulcers can destroy vision if not treated early. Two seriously ill patients developed corneal infections with Pseudomonas aeruginosa while in the pediatric intensive care unit. In one patient the eye was destroyed. The other patient was treated successfully, but early intervention was crucial.

Matrix Metalloproteinase-28 Deletion Exacerbates Cardiac Dysfunction and Rupture Following Myocardial Infarction in Mice by Inhibiting M2 Macrophage Activation

Rationale: Matrix metalloproteinase (MMP)-28 regulates the inflammatory and extracellular matrix responses in cardiac aging, but the roles of MMP-28 after myocardial infarction (MI) have not been explored. Objective: To determine the impact of MMP-28 deletion on post-MI remodeling of the left ventricle (LV). Methods and Results: Adult C57BL/6J wild-type (n=76) and MMP null (MMP-28−/−, n=86) mice of both sexes were subjected to permanent coronary artery ligation to create MI. MMP-28 expression decreased post-MI, and its cell source shifted from myocytes to macrophages. MMP-28 deletion increased day 7 mortality because of increased cardiac rupture post-MI. MMP-28−/− mice exhibited larger LV volumes, worse LV dysfunction, a worse LV remodeling index, and increased lung edema. Plasma MMP-9 levels were unchanged in the MMP-28−/− mice but increased in wild-type mice at day 7 post-MI. The mRNA levels of inflammatory and extracellular matrix proteins were attenuated in the infarct regions of MMP-28−/− mice, indicating reduced inflammatory and extracellular matrix responses. M2 macrophage activation was impaired when MMP-28 was absent. MMP-28 deletion also led to decreased collagen deposition and fewer myofibroblasts. Collagen cross-linking was impaired as a result of decreased expression and activation of lysyl oxidase in the infarcts of MMP-28−/− mice. The LV tensile strength at day 3 post-MI, however, was similar between the 2 genotypes. Conclusions: MMP-28 deletion aggravated MI-induced LV dysfunction and rupture as a result of defective inflammatory response and scar formation by suppressing M2 macrophage activation.

Contrast induced‐acute kidney injury following peripheral angiography with carbon dioxide versus iodinated contrast media: A meta‐analysis and systematic review of current literature

We conducted a meta‐analysis to compare the incidence of acute kidney injury (AKI) with carbon dioxide (CO2) versus iodinated contrast media (ICM).